Summary
A considerable amount of information is now available concerning the clinical pharmacology of the anticonvulsant drugs. Some of the more important data are reviewed in this article.
In recent years, valproic acid (or sodium valproate) has found a place as a major anticonvulsant agent, while older drugs such as troxidone and sulthiame seem to be disappearing from use. Although much information is available, the essential mechanisms of action of the anticonvulsant drugs are still not understood, either at a molecular or at an electrophysiological level. The pharmacokinetics of the anticonvulsants in common use are now reasonably well documented, though some minor questions are still to be answered. Numerous interactions between anticonvulsants and endogenous substances or other drugs administered concurrently (including other anticonvulsants) have been recorded, but much work still needs to be done to elucidate the frequency and mechanisms of the various interactions. Many adverse effects of the anticonvulsants are known, but further unwanted effects of long-established drugs continue to emerge from time to time, including the still somewhat controversial matter of anticonvulsant-related dysmorphogenesis. The use of valproic acid and its sodium salt has been associated with a worrying incidence of serious liver and pancreatic toxicity.
Adequate basic data are now available to put the clinical use of anticonvulsants on a rational basis, but much work remains to be done in this area. In particular, the question of ‘therapeutic ranges’ of plasma concentrations of the various drugs needs to be reinvestigated in a rigorous statistical fashion, and in relation to different clinical types of epilepsy. The usefulness of monitoring free rather than total drug concentrations also needs further investigation. The ultimate test of the validity of all background scientific pharmacological information about anticonvulsants is its usefulness in the treatment of patients with epilepsy.
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References
Aarli, J.A.: Drug-induced IgA deficiency in epileptic patients. Archives of Neurology 33: 296–299 (1976).
Aarli, J.A. and Tonder, O.: Effect of antiepileptic drugs on serum and salivary IgA. Scandinavian Journal of Immunology 4: 391–396 (1975).
Aarskog, D.: Association between maternal intake of diazepam and oral clefts. Lancet 2: 921 (1975).
Adams, DJ.; Luders, H. and Pippenger, C: Sodium valproate in the treatment of intractable seizure disorders: A clinical and electroencephalographic study. Neurology 28: 152–157 (1978).
Agarwal, B.N.; Cabebe, F.G. and Hoffman, B.I.: Diphenylhydantoin induced acute renal failure. Nephron 18: 249–251 (1977).
Ahmad, S.; Clarke, L; Hewett, A.J. and Richens, A.: Controlled trial of frusemide as an antiepileptic drug in focal epilepsy. British Journal of Clinical Pharmacology 3: 621–625 (1976).
Allen, J.P.; Ludden, T.M.; Burrow, S.R.; Clementi, W.A. and Stavchansky, S.A.: Phenytoin cumulation kinetics. Clinical Pharmacology and Therapeutics 26: 445–448 (1979).
Anderson, E.G.; Markowitz, S.D. and Bonnycastle, D.D.: Brain 5-hydroxytryptamine and anticonvulsant activity. Journal of Pharmacology and Experimental Therapeutics 136: 179–182 (1962).
Angelopoulos, A.P. and Goaz, P.W.: Incidence of diphenylhydantoin gingival hyperplasia. Oral Surgery 34: 898–906 (1972).
Annegers, J.F.; Elveback, L.R.; Hauser, W.A. and Kurland, L.T.: Do anticonvulsants have a teratogenic effect. Archives of Neurology 31: 364–373 (1974).
Argülles, A.E. and Rosner, J.: Diazepam and plasma-testosterone levels. Lancet 2: 607 (1975).
Arnold, K. and Gerber, N.: The rate of decline of diphenylhydantoin in human plasma. Clinical Pharmacology and Therapeutics 11: 121–134(1970).
Asconapé, J.J. and Penry, J.K.: Use of antiepileptic drugs in the presence of liver and kidney diseases: A review. Epilepsia 23 (Suppl. 1): S65–S79 (1982).
Ayala, G.F.; Lin, S. and Johnston, D.: The mechanism of action of diphenylhydantoin on invertebrate neurons. I. Effects on basic membrane properties. Brain Research (Amsterdam) 121: 245–258 (1977).
Ayala, G.F. and Johnston, D.: The influence of phenytoin on the fundamental electrical properties of simple neural systems. Epilepsia 18: 288–307 (1977).
Ballek, R.E.; Reidenberg, M.M. and Orr, L.: Inhibition of diphenylhydantoin metabolism by chloramphenicol. Lancet 1: 150(1973).
Bartels, H.; Günther, E. and Wallis, S.: Flow-dependent salivary primidone levels in epileptic children. Epilepsia 20: 431–436 (1979).
Barth, N.; Alvan, G.; Borgå, O. and Sjöqvist, F.: Twofold inter-individual variation in plasma protein binding of phenytoin in patients with epilepsy. Clinical Pharmacokinetics 1: 444–452 (1976).
Batalden, P.B.; Van Dyne, B.J. and Cloyd, J.: Pancreatitis associated with valproic acid therapy. Pediatrics 64: 520–522 (1979).
Battino, D.; Avanzini, G.; Bossi, L.; Croci, D.; Cusi, C; Gomeni, C. and Moise, A.: Plasma levels of primidone and its metabolite phenobarbital: Effect of age and associated therapy. Therapeutic Drug Monitoring 5: 73–79 (1983).
Battino, D.; Bossi, L.; Croci, D.; Franceschetti, S.; Gomeri, C; Moise, A. and Vitali, A.: Carbamazepine plasma levels in children and adults: Influence of age, dose, and associated therapy. Therapeutic Drug Monitoring 2: 315–322 (1980).
Bauer, L.A. and Blouin, R.A.: Age and phenytoin kinetics in adult epileptics. Clinical Pharmacology and Therapeutics 31: 301–304 (1982).
Baumel, I.P.; Gallagher, B.B. and Mattson, R.H.: Phenylethylmalonamide (PEMA). An important metabolite of primidone. Archives of Neurology 27: 34–41 (1972).
Bourgeois, B.F.D.; Dodson, W.E. and Ferrendelli, J.A.: Interaction between primidone, carbamazepine, and nicotinamide. Neurology 32: 1122–1126 (1982).
Baylis, E.M.; Crowley, J.M.; Preece, J.M.; Sylvester, P.E. and Marks, V.: Influence of folic acid on blood-phenytoin levels. British Medical Journal 1: 62–64 (1971).
Beernink, D.H. and Miller III, J.J.: Anticonvulsant induced anti-nuclear antibodies and lupus like disease in children. Journal of Pediatrics 82: 113–117 (1973).
Berlin, A. and Dahlström, H.: Pharmacokinetics of the anticonvulsant drug clonazepam evaluated from single oral and intravenous doses and by repeated oral administration. European Journal of Clinical Pharmacology 9: 155–159 (1975).
Bertilsson, L.: Clinical pharmacokinetics of carbamazepine. Clinical Pharmacokinetics 3: 128–143 (1978).
Bochner, F.; Hooper, W.D.; Sutherland, J.M.; Eadie, M.J. and Tyrer, J.H.: Diphenylhydantoin concentrations in saliva. Archives of Neurology 31: 57–59 (1974).
Bochner, F.; Hooper, W.D.; Tyrer, J.H. and Eadie, M.J.: Factors involved in an outbreak of phenytoin intoxication. Journal of the Neurological Sciences 16: 481–487 (1972).
Bodensteiner, J.B.; Morris, H.H. and Golden, G.S.: Asterixis associated with sodium valproate. Neurology 31: 194–195 (1981).
Booker, H.E.: Idiosyncratic reactions to the antiepileptic drugs. Epilepsia 16: 171–181 (1975).
Booker, H.E.; Hosokowa, K.; Burdette, R.D. and Darcey, B.: A clinical study of serum primidone levels. Epilepsia 11: 395–402 (1970).
Botez, M.I. and Reynolds, E.H. (Eds): Folic Acid in Neurology, Psychiatry and Internal Medicine (Raven Press, New York 1979).
Bowdle, T.A.; Levy, R.H. and Cutler, R.E.: Effect of carbamazepine on valproic acid clearance in normal man. Clinical Pharmacology and Therapeutics 25: 215 (1979).
Bowdle, T.A.; Patel, I.H.; Levy, R.H. and Wilensky, A.J.: Valproic acid dosage and plasma protein binding and clearance. Clinical Pharmacology and Therapeutics 28: 486–492 (1980).
Braithwaite, R.A.; Flanagan, R.J. and Richens, A.: Steady state plasma nortriptyline concentrations in epileptic patients. British Journal of Clinical Pharmacology 2: 469–471 (1975).
Breimer, D.D.; Bracht, H. and De Boer, A.G.: Plasma level profile of nitrazepam (Mogadon®) following oral administration. British Journal of Clinical Pharmacology 4: 709–711 (1977).
Brennan, R.W.; Dehejia, H.; Kutt, H.; Verebely, K. and McDowell, F.: Diphenylhydantoin intoxication attendant to slow inactivation of isoniazid. Neurology 20: 687–693 (1970).
Brillman, J.; Gallagher, B.B. and Mattson, R.H.: Acute primidone intoxication. Archives of Neurology 30: 255–258 (1974).
Browne, T.R.; Dreifuss, F.E.; Dyken, P.R.; Goode, D.J.; Penry, J.K.; Porter, R.J.; White, B.G. and White, P.I.: Ethosuximide in the treatment of absence (petit mal) seizures. Neurology 25: 515–524(1975).
Bryson, S.M.; Verma, N.; Scott, P.J.W. and Rubin, P.C.: Pharmacokinetics of valproic acid in young and elderly subjects. British Journal of Clinical Pharmacology 16: 104–105 (1983).
Buchanan, R.A.; Fernandel, L. and Kinkel, A.W.: Absorption and elimination of ethosuximide in children. Journal of Clinical Pharmacology 9: 393–398 (1969).
Buchanan, R.A.; Kinkel, A.W. and Smith, T.C.: The absorption and excretion of ethosuximide. International Journal of Clinical Pharmacology 7: 213–218 (1973).
Buchthal, F. and Lennox-Buchthal, M.A.: Phenobarbital. Relation of serum concentration to control of seizures; in Wood-bury et al. (Eds) Antiepileptic Drugs, pp. 335–343 (Raven Press, New York 1972).
Burstein, S. and Klaiber, E.L.: Phenobarbital induced increase in 6 betahydroxycortisol excretion: Clue to its significance in human urine. Journal of Clinical Endocrinology and Metabolism 25: 293 (1965).
Butler, T.C.: Quantitative studies on the metabolic fate of mephobarbital (N-methyl phenobarbital). Journal of Pharmacology and Experimental Therapeutics 106: 235–245 (1952).
Butler, T.C.: The metabolic hydroxylation of phenobarbital. Journal of Pharmacology and Experimental Therapeutics 116: 326–336 (1956).
Butler, T.C.: The metabolic conversion of 5,5-diphenylhydantoin to 5-(p-hydroxyphenyl)-5-phenylhdantoin. Journal of Pharmacology and Experimental Therapeutics 119: 1–11 (1957).
Butler, T.C.; Makaffee, C. and Waddell, W.J.: Phenobarbital: Studies of elimination, accumulation, tolerance and dosage schedules. Journal of Pharmacology and Experimental Therapeutics 111: 425–435(1954).
Butler, T.C. and Waddell, W.J.: Metabolic conversion of primidone (Mysoline) to phenobarbital. Proceedings of the Society for Experimental Biology and Medicine 93: 544–546 (1956).
Cantu, R.C. and Schwab, R.S.: Ceruloplasmin rise and PBI fall in serum due to diphenylhydantoin. Archives of Neurology 15: 393–396 (1966).
Cantu, R.C; Schwab, R.S. and Timberlake, W.H.: Comparison of blood levels with oral and intramuscular diphenylhydantoin. Neurology 18: 782–784 (1968).
Cereghino, J.J.; Brock, J.T.; Van Meter, J.C.; Penry, J.K.; Smith, L.D. and White, B.G.: The efficacy of carbamazepine combinations in epilepsy. Clinical Pharmacology and Therapeutics 18: 733–741 (1975).
Chadwick, D.; Jenner, P. and Reynolds, E.H.: Amines, anticonvulsants and epilepsy. Lancet 1: 1425–1426 (1975).
Chadwick, D.; Reynolds, E.H. and Marsden, CD.: Anticonvulsant-induced dyskinesias: A comparison with dyskinesias induced by neuroleptics. Journal of Neurology, Neurosurgery and Psychiatry 39: 1210–1218 (1976).
Chalazonitis, N. and Arvanitaki, A.: Convulsants and anticonvulsants on single neurons; in Mercier (Ed.) Anticonvulsant Drugs. International Encyclopaedia of Pharmacology and Therapeutics, Section 19, 2: 401–424 (Pergamon Press, Oxford 1973).
Chang, T.; Dill, W.A. and Glazko, A.J.: Ethosuximide: Absorption, distribution and excretion; in Woodbury et al. (Eds) Antiepileptic Drugs, pp. 417–423 (Raven Press, New York 1972).
Chapron, D.J.; Kramer, P.A.; Mariano, S.L. and Hohnadel, D.C.: Effect of calcium and antacids on phenytoin bioavailability. Archives of Neurology 36: 436–438 (1979).
Choi, Y.; Thrasher, K.; Werk Jr, E.E.; Sholiton, L.J. and Olinger, C: Effect of diphenylhydantoin on cortisol kinetics in humans. Journal of Pharmacology and Experimental Therapeutics 176: 27–34 (1971).
Chou, D.T. and Wang, S.C: Unit activity of amygdala and hippocampal neurons: Effects of morphine and benzodiazepines. Brain Research 126: 427–440 (1977).
Christensen, L.K. and Skovsted, L.: Inhibition of drug metabolism by chloramphenicol. Lancet 2: 1397–1399 (1969).
Christiansen, J. and Dam, M.: Influence of phenobarbital and diphenylhydantoin on plasma carbamazepine levels in patients with epilepsy. Acta Neurologica Scandinavica 49: 543–546 (1973).
Christiansen, C; Redbro, P. and Tjellesen, L.: Pathophysiology behind anticonvulsant osteomalacia. Acta Neurologia Scandinavica 67 (Suppl. 94): 21–28 (1983).
Cloyd, J.C.; Miller, K.W. and Leppik, I.E.: Primidone kinetics: Effect of concurrent drugs and duration of therapy. Clinical Pharmacology and Therapeutics 29: 402–407 (1981).
Conney, A.H.: Pharmacological implications of microsomal enzyme induction. Pharmacology Reviews 19: 317–366 (1967).
Cook, CE.; Amerson, E.: Poole, W.K.; Lesser, P. and O’Tauma, L.: Phenytoin and phenobarbital concentrations in saliva and plasma measured by radioimmunoassay. Clinical Pharmacology and Therapeutics 18: 742–747 (1975).
Cotter, L.M.; Eadie, M.J.; Hooper, W.D.; Lander, CM.; Smith, G.A. and Tyrer, J.H.: The pharmacokinetics of carbamazepine. European Journal of Clinical Pharmacology 12: 451–456 (1977).
Cotter, L.M.; Smith, G.A.; Hooper, W.D.; Tyrer, J.H. and Eadie, M.J.: The bioavailability of carbamazepine. Proceedings of the Australian Association of Neurologists 12: 123–128 (1975).
Coulter, D.L. and Allen, R.J.: Pancreatitis associated with valproic acid therapy for epilepsy. Annals of Neurology 7: 92 (1980).
Coulter, D.L. and Allen, R.J.: Hyperammonemia with valproic acid therapy. Journal of Pediatrics 99: 317–319 (1981).
Cranford, R.E.; Leppik, I.E.; Patrick, B.; Anderson, C.B. and Kostick, B.: Intravenous phenytoin: Clinical and pharmacokinetic aspects. Neurology 27: 376 (1977).
Cucinell, S.A.; Conney, A.H.; Sansur, M. and Burns, J.J.: Drug interactions in man. I. Lowering effect of phenobarbital on plasma levels of bishydroxycoumarin (Dicumarol) and diphenylhydantoin (Dilantin). Clinical Pharmacology and Therapeutics 6: 420–429 (1965).
Dam, M.; Christiansen, J.; Munck, O. and Mygind, K.I.: Antiepileptic drugs: Metabolism in pregnancy. Clinical Pharmacokinetics 4: 53–62 (1979).
Dam, M.; Kristensen, C.B.; Hansen, B.S. and Christiansen, J.: Interaction between carbamazepine and propoxyphene in man. Acta Neurologica Scandinavica 56: 603–607 (1977).
Dam, M.; Mygind, K.I. and Christiansen, J.: Antiepileptic drugs plasma clearance during pregnancy; in Janz (Ed.) Epileptology, pp. 179–183 (Thieme, Stuttgart 1976).
Danks, D.M.; Barry, J.E. and Sheffield, L.J.: Digital hypoplasia and anticonvulsants during pregnancy. Journal of Pediatrics 85: 877 (1974).
Danner, R.: Electrophysiological effects of diphenylhydantoin and carbamazepine on the peripheral and central nervous system. Acta Neurologica Scandinavica 65: 668–680 (1982).
Davies, J.E.; Edmundson, W.F.; Carter, C.H. and Barquet, A.: Effect of anticonvulsant drugs on dicophane (D.D.T.) residues in man. Lancet 2: 7–9 (1969).
Davis, R.E. and Woodliff, HJ.: Folic acid deficiency in patients receiving anticonvulsant drugs. Medical Journal of Australia 2: 1070–1072 (1971).
Dean, M.; Stock, B.; Patterson, R.J. and Levy, G.: Serum protein binding of drugs during and after pregnancy in humans. Clinical Pharmacology and Therapeutics 28: 253–261 (1980).
de Boer, A.G.; Moolenaar, F.; de Leede, L.G.J. and Breimer, D.D.: Rectal drug administration: Clinical pharmacokinetic considerations. Clinical Pharmacokinetics 7: 285–311 (1982).
de Gier, J.J.; t’Hart, B.J.; Wilderink, P.F. and Nelemans, F.A.: Comparison of plasma and saliva levels of diazepam. British Journal of Clinical Pharmacology 10: 151–155 (1980).
De Leacy, E.A.; McLeay, CD.; Eadie, M.J. and Tyrer, J.H.: Effects of subjects sex and intake of tobacco, alcohol and oral contraceptives on plasma phenytoin levels. British Journal of Clinical Pharmacology 8: 33–36 (1979).
Dent, CE.; Richens, A.; Rowe, D.J.F. and Stamp, T.C.B.: Osteomalacia with long-term anticonvulsant therapy in epilepsy. British Medical Journal 4: 69–72 (1970).
Deupree, J.D.: Mode of action of anticonvulsant drugs: Membrane effect; in Tyrer (Ed.) The Treatment of Epilepsy, pp. 1–28 (MTP Press, Lancaster 1980).
Dhillon, S. and Richens, A.: Bioavailability of rectally-administered diazepam in adult epileptic patients. British Journal of Clinical Pharmacology 11: 437P-438P (1981).
Dhillon, S. and Richens, A.: Valproic acid and diazepam interaction in vivo. British Journal of Clinical Pharmacology 13: 553–560(1982).
Di Gregorio, G.I.; Piraino, A.J. and Ruch, E.: Diazepam concentrations in parotid saliva, mixed saliva and plasma. Clinical Pharmacology and Therapeutics 24: 720–725 (1978).
Di Salle, E.; Pacifici, G.M. and Morselli, P.L.: Studies on plasma protein binding of carbamazepine. Pharmacology Research Communications 6: 193–202 (1974).
Dreifuss, F.E.; Penry, J.K.; Rose, S.W.; Kupferberg, H.J.; Dyken, P. and Sato, S.: Serum clonazepam concentrations in children with absence seizures. Neurology 25: 255–258 (1975).
Driessen, O.; Hoppener, R.J. and Van Der Velde, E.A.: Practical and theoretical aspects of phenytoin administration. I. Relationship between dose and plasma concentration. European Neurology 19: 353–365 (1980).
Eadie, M.J.: Which anticonvulsant drug? Drugs 17: 213–218 (1979).
Eadie, M J.: Pharmacokinetics of the anticonvulsant drugs; in Tyrer (Ed.) The Treatment of Epilepsy, pp. 61–93 (MTP Press, Lancaster 1980a).
Eadie, M.J.: Unwanted effects of anticonvulsant drugs; in Tyrer (Ed.) The Treatment of Epilepsy, pp. 129–160 (MTP Press, Lancaster 1980b).
Eadie, M.J.: Metabolism of anticonvulsant drugs. Reviews on Drug Metabolism and Drug Interaction 3: 317–347 (1981).
Eadie, M J.; Bochner, F.; Hooper, W.D. and Tyrer, J.H.: Preliminary observations on the pharmacokinetics of methylpheno-barbitone. Clinical and Experimental Neurology 15: 131–144 (1978).
Eadie, M.J.; Lander, CM.; Hooper, W.D. and Tyrer, J.H.: The effects of phenobarbitone dose on plasma phenobarbitone levels in epileptic patients. Proceedings of the Australian Association of Neurologists 13: 89–96 (1976a).
Eadie, M J.; Lander, CM.; Hooper, W.D. and Tyrer, J.H.: Factors influencing plasma phenobarbitone levels in epileptic patients. British Journal of Clinical Pharmacology 4: 541–547 (1977a).
Eadie, M.J.; Lander, J.M. and Tyrer, J.H.: Plasma drug level monitoring in pregnancy. Clinical Pharmacokinetics 2: 427–436 (1977c).
Eadie, MJ. and Tyrer, J.H.: Anticonvulsant Therapy: Pharmacological Basis and Practice, 2nd edition (Churchill Livingstone, London, Edinburgh and New York 1980).
Eadie, M.J.; Tyrer, J.H.; Bochner, F. and Hooper, W.D.: The elimination of phenytoin in man. Clinical and Experimental Pharmacology and Physiology 3: 217–224 (1976b).
Eadie, M.J.; Tyrer, J.H. and Hooper, W.D.: Diphenylhydantoin dosage. Proceedings of the Australian Association of Neurologists 10: 53–59 (1973).
Eadie, MJ.; Tyrer, J.H.; Smith, G.A. and McKauge, L.: Pharmacokinetics of drugs used for petit mal absence epilepsy. Clinical and Experimental Neurology 14: 172–183 (1977b).
Eatman, F.B.; Colburn, W.A.; Boxenbaum, H.G.; Posmanter, H.N.; Weinfeld, R.E.; Ronfeld, R.; Weissman, L.; Moore, J.D.; Gibaldi, M. and Kaplan, S.A.: Pharmacokinetics of diazepam following multiple-dose oral administration to healthy human subjects. Journal of Pharmacokinetics and Biopharmaceutics 5: 481–494 (1977).
Edwards, V.E. and Eadie, M J.: Clonazepam — a clinical study of its effectiveness as an anticonvulsant. Proceedings of the Australian Association of Neurologists 10: 61–66 (1973).
Eeg Olofsson, O.: Experience with Rivotril (clonazepam, Ro 5 4023 ) in treatment of epilepsy, particularly minor motor epilepsy, in mentally retarded children. Epilepsia 14: 78–79 (1973).
Ehrnebo, M.; Agurell, S.; Jailing, B. and Boreus, L.O.: Age differences in drug binding by plasma proteins: Studies on human foetuses, neonates and adults. European Journal of Clinical Pharmacology 3: 189–193 (1971).
Ehrenbo, M. and Odar-Cederlöf, I.: Binding of amobarbital, pentobarbital and diphenylhydantoin to blood cells and plasma proteins in healthy volunteers and uraemic patients. European Journal of Clinical Pharmacology 8: 445–453 (1975).
Eichelbaum, M.; Bertilsson, L.; Lund, L.; Palmer, L. and Sjöqvist, F.: Plasma levels of carbamazepine and carbamazepine-10,11-epoxide during carbamazepine therapy in epileptic patients. European Journal of Clinical Pharmacology 9: 417–421 (1976).
Eichelbaum, M.; Ekbom, K.; Bertilsson, L.; Ringberger, V.A. and Rane, A.: Plasma kinetics of carbamazepine and its epoxide metabolite in man after single and multiple doses. European Journal of Clinical Pharmacology 8: 337–341 (1975).
Eichelbaum, M.; Köthe, K.W.; Hoffman, F. and von Unruh, G.E.: Use of stable labelled carbamazepine to study its kinetics during chronic carbamazepine treatment. European Journal of Clinical Pharmacology 23: 241–244 (1982).
Englander, R.N.; Johnson, R.N.; Brickley, J.J. and Hanna, G.R.: Effect of antiepileptic drugs on thalamocortical excitability. Neurology 27: 1134–1139(1977).
Erkkola, R. and Kanto, J.: Diazepam and breast feeding. Lancet 1: 1235–1236 (1972).
Eschenhof, V.E.: Untersuchungen uber das Schicksal des Anticonvulsivums Clonazepam in Organismus der Ratte, des Hundes und des Menchen. Arzneimittel-Forschung 23: 390–400 (1973).
Espir, M.L.E.; Benton, P.; Will, E.; Hayes, M.J. and Walker, G.: Sodium valproate (Epilim) — some clinical and pharmacological aspects; in Legg (Ed.) Clinical and Pharmacological Aspects of Sodium Valproate (Epilim) in the Treatment of Epilepsy, pp. 145–151 (MLS Consultants, Tunbridge Wells 1976).
Esplin, D.W.: Effect of diphenylhydantoin on synaptic transmission in cat spinal cord and stellate ganglion. Journal of Pharmacology and Experimental Therapeutics 120: 301–323 (1957).
Faigle, J.W. and Feldmann, K.F.: Pharmacokinetic data of carbamazepine and its major metabolites in man; in Schneider et al. (Eds) Clinical Pharmacology of Antiepileptic Drugs, pp. 159–165 (Springer, Berlin 1975).
Falconer, M.A. and Davidson, S.: Coarse features in epilepsy as a consequence of anticonvulsant therapy. Drugs 7: 394–395 (1974).
Feldman, G.L.; Weaver, D.D. and Lovrien, D.W.: The foetal trimethadione syndrome. American Journal of Diseases of Childhood 131: 1389–1392 (1977).
Figueroa, A.M.; Johnson, R.H.; Lambie, D.G. and Shakir, R.A.: The role of folate deficiency in the development of peripheral neuropathy caused by anticonvulsants. Journal of the Neurological Sciences 48: 315–323 (1980).
Fincham, R.W.; Wiley, D.E. and Schottelius, D.D.: Use of phenytoin serum levels in a case of status epilepticus. Neurology 26: 879–881 (1976).
Finucane, J.F. and Griffiths, R.S.: Effect of phenytoin therapy on thyroid function. British Journal of Clinical Pharmacology 3: 1041–1044 (1976).
Fossan, G.O.: Reduced CSF IgG in patients treated with phenytoin diphenylhydantoin). European Neurology 14: 426–432 (1976).
Frantzen, E.; Hansen, J.M.; Hansen, O.E. and Kristensen, M.: Phenytoin (Dilantin®) intoxication. Acta Neurologica Scandinavica 43: 440–446 (1967).
Fredholm, B.B.; Rane, A. and Persson, B.: Diphenylhydantoin binding to proteins in plasma and its dependence on free fatty acid and bilirubin concentration in dogs and newborn infants. Pediatric Research 9: 26–30 (1975).
Frigerio, A. and Morselli, P.L.: Carbamazepine: Biotransformation; in Penry and Daly (Eds) Advances in Neurology, Vol. 11, pp. 295–307 (Raven Press, New York 1975).
Frigo, G.M.; Lecchini, S.; Gatti, G.; Perucca, E. and Crema, A.: Modification of phenytoin clearance by valproic acid in normal subjects. British Journal of Clinical Pharmacology 8: 553–556 (1979).
Friis, M.L.: Epilepsy among parents of children with facial clefts. Epilepsia 20: 69–76 (1979).
Friis, M.L.; Broeng-Neilsen, B.; Sindrup, E.H.; Lund, M.; Fogh-Andersen, P. and Hague, M.: Facial clefts among epileptic patients. Archives of Neurology 38: 227–229 (1981).
Fuccella, L.M.; Bolcioni, G.; Tamassia, V.; Ferrario, L. and Tognoni, G.: Human pharmacokinetics and bioavailability of temazepam administered in soft gelatin capsules. European Journal of Clinical Pharmacology 12: 383–386 (1977).
Gallagher, B.B. and Baumel, I.P.: Primidone. Absorption, distribution and excretion; in Woodbury et al. (Eds) Antiepileptic Drugs, pp. 357–359 (Raven Press, New York 1972).
Garnett, W.R.; Carter, B.L. and Pellock, J.M.: Effect of calcium and antacids on phenytoin bioavailability. Archives of Neurology 37: 467 (1980).
Garrettson, L.K. and Dayton, P.G.: Disappearance of phenobarbital and diphenylhydantoin from serum of children. Clinical Pharmacology and Therapeutics 11: 674–679 (1970).
Garrettson, L.K. and Jusko, W.J.: Diphenylhydantoin elimination kinetics in overdosed children. Clinical Pharmacology and Therapeutics 17: 481–491 (1975).
Garrettson, L.K.; Perel, J.M. and Dayton, P.G.: Methylphenidate interaction with both anticonvulsants and ethyl biscoumacetate. Journal of the American Medical Association 207: 2053–2056 (1969).
Gérardin, A.P.; Abadie, F.V.; Campestrini, J.A. and Theobald, W.: Pharmacokinetics of carbamazepine in normal humans after single and repeated oral doses. Journal of Pharmacokinetics and Biopharmaceutics 4: 521–535 (1976).
Gerber, N.; Dickinson, R.G.; Harland, R.C.; Lynn, R.K.; Houghton, D.; Antonias, J.I. and Schimschock, J.C.: Reye-like syndrome associated with valproic acid therapy. Journal of Pediatrics 95: 142–144 (1979).
Geller, H.M.; Hoffer, B.J. and Taylor, D.A.: Electrophysiological actions of benzodiazepines. Federation Proceedings 39: 3016–3023 (1980).
Gerber, N. and Wagner, J.G.: Explanation of the dose-dependent decline of diphenylhydantoin plasma levels by fitting to the integrated form of the Michaelis-Menten equation. Research Communications in Chemical Pathology and Pharmacology 3: 455–466 (1972).
German, J.; Kowal, A. and Ehlers, K.H.: Trimethadione and human teratogenesis. Teratology 3: 349–362 (1970).
Giles, H.G.; Zilm, D.H.; Frecker, R.C.; MacLeod, S.M. and Sellers, E.M.: Saliva and plasma concentrations of diazepam after a single oral dose. British Journal of Clinical Pharmacology 4: 711–712 (1977).
Glaser, G.H.; Penry, J.K. and Woodbury, D.M. (Eds): Antiepileptic drugs: Mechanisms of action. Advances in Neurology 27: 1–728 (Raven Press, New York 1980).
Glazko, A.J.: Antiepileptic drugs: Biotransformation, metabolism and serum half-life. Epilepsia 16: 367–391 (1975).
Glazko, A.J.; Chang, T.; Baukema, J.; Dill, W.A.; Goulet, J.R. and Buchanan, R.A.: Metabolic disposition of diphenylhydantoin in normal human subjects following intravenous administration. Clinical Pharmacology and Therapeutics 10: 498–504 (1969).
Goldbaum, L.R. and Smith, P.K.: The interaction of barbiturates with serum albumin and its possible relation to their disposition and pharmacological actions. Journal of Pharmacology and Experimental Therapeutics 111: 197–209 (1954).
Goldberg, E.M. and Sanbar, S.S.: Hyperglycemic, nonketotic coma following administration of Dilantin (diphenylhydantoin). Diabetes 18: 101–106 (1969).
Gordon, A.S.; Milfay, D. and Diamond, I.: Phosphorylation of membrane-bound acetylcholine receptor. Inhibition by diphenylhydantoin. Annals of Neurology 5: 201–203 (1979).
Goulet, J.R.; Kinkel, A.W. and Smith, T.C.: Metabolism of ethosuximide. Clinical Pharmacology and Therapeutics 20: 213–218 (1976).
Graham, J.: A comparison of the absorption of phenobarbitone given via the oral and the intramuscular route. Clinical and Experimental Neurology 15: 154–158 (1978).
Gram, L.; Wulff, K.; Rassmussen, K.E.; Flachs, H.; Wurtz-Jorgensen, A.; Sommerbeck, K.W. and Lohren, V.: Valproate sodium: A controlled clinical trial including monitoring of drug levels. Epilepsia 18: 141–148 (1977).
Greenblatt, D.J.; Allen, M.D.; Harmatz, J.S. and Shader, R.I.: Diazepam disposition determinants. Clinical Pharmacology and Therapeutics 27: 301–312 (1980).
Greenblatt, D.J.; Allen, M.D.; MacLaughlin, D.S.; Harmatz, J.S. and Shader, R.K.: Diazepam absorption: Effect of antacids and food. Clinical Pharmacology and Therapeutics 24: 600–609 (1978).
Gropper, A.L.: Diphenylhydantoin sensitivity. Report of fatal case with hepatitis and exfoliative dermatitis. New England Journal of Medicine 254: 522–523 (1956).
Guelen, P.J.M.; Van Der Kleijn, E. and Woudstra, U.: Statistical analysis of pharmacokinetic parameters in epileptic patients chronically treated with anti-epileptic drugs; in Schneider et al. (Eds) Clinical Pharmacology of Anti-epileptic Drugs, pp. 2–10 (Springer, Berlin 1975).
Gugler, R.; Manion, C.V. and Azarnoff, D.L.: Phenytoin: Pharmacokinetics and bioavailability. Clinical Pharmacology and Therapeutics 19: 135–142 (1976).
Gugler, R. and Mueller, G,: Plasma protein binding of valproic acid in healthy subjects and in patients with renal disease. British Journal of Clinical Pharmacology 5: 441–446 (1978).
Gugler, R.; Schell, A.; Eichelbaum, A.; Froscher, W. and Schulz, H.-U.: Disposition of valproic acid in man. European Journal of Clinical Pharmacology 12: 125–132 (1977).
Gugler, R. and von Unruh, G.E.: Clinical pharmacokinetics of valproic acid. Clinical Pharmacokinetics 5: 67–83 (1980).
Haigh, D. and Forsythe, W.I.: The treatment of childhood epilepsy with sodium valproate. Developmental Medicine and Child Neurology 17: 743–748 (1975).
Hallstrom, C; Lader, M.H. and Curry, S.H.: Diazepam and N-desmethyldiazepam concentrations in saliva, plasma and CSF. British Journal of Clinical Pharmacology 9: 333–339 (1980).
Hansen, J.M.; Kristensen, M. and Skovsted, L.: Sulthiame (Ospolot) as inhibitor of diphenylhydantoin metabolism. Epilepsia 9: 17–22(1968).
Hansen, J.M.; Kristensen, M.; Skovsted, L. and Christensen, L.K.: Dicoumarol-induced diphenylhydantoin intoxication. Lancet 2: 265–266 (1966).
Hansen, J.M.; Siersbaek-Nielsen, A.; Kristensen, M.; Skovsted, L. and Christensen, L.K.: Effect of diphenylhydantoin on the metabolism of dicoumarol in man. Acta Medica Scandinavica 189: 15–19 (1971a).
Hansen, J.M.; Siersbaek-Nielsen, K. and Skovsted, L.: Carbamazepine-induced acceleration of diphenylhydantoin and warfarin metabolism in man. Clinical Pharmacology and Therapeutics 12: 539–543 (1971b).
Hansson, O. and Sillanpaa, M.: Pyridoxine and serum concentrations of phenytoin and phenobarbitone. Lancet 1: 256 (1976).
Hazlett, D.R.; Ward Jr, G.W. and Madison, D.S.: Pulmonary function loss in diphenylhydantoin therapy. Chest 66: 660–664 (1974).
Hayes, M.J.; Langman, M.J.S. and Short, A.H.: Changes in drug metabolism with increasing age. 2. Phenytoin clearance and protein binding. British Journal of Clinical Pharmacology 2: 73–79 (1975).
Hegarty, J.E. and Dundee, J.W.: Sequelae after intravenous injection of three benzodiazepines — diazepam, lorazepam and flunitrazepam. British Medical Journal 2: 1384–1385 (1977).
Henry, D.A.; Lawson, D.H.; Reavey, P. and Renfrew, S.: Hyponatraemia during carbamazepine treatment. British Medical Journal 1: 83–84 (1977).
Hillestad, L.; Hansen, T.; Melsom, H. and Drivenes, A.: Diazepam metabolism in normal man. I. Serum concentrations and clinical effects after intravenous, intramuscular, and oral administration. Clinical Pharmacology and Therapeutics 16: 479–484 (1974).
Hoffman, F.; von Unruh, G.E. and Jancik, B.C.: Valproic acid disposition in epileptic patients during combined antiepileptic maintenance therapy. European Journal of Clinical Pharmacology 19: 383–385 (1981).
Holmes, E.L. and Une, A.Z. (1965). cited in Chang, T.; Dill, W.A. and Glazko, A.J.: Ethosuximide: Absorption, distribution and excretion; in Woodbury et al. (Eds) Antiepileptic Drugs pp. 417–423 (Raven Press, New York 1972).
Hooper, W.D.; Bochner, F.; Eadie, M.J. and Tyrer, J.H.: Plasma protein binding of diphenylhydantoin. Effects of sex hormones, renal and liver disease. Clinical Pharmacology and Therapeutics 15: 276–282 (1974a).
Hooper, W.D.; Du Betz, D.K.; Bochner, F.; Cotter, L.M.; Smith, G.A.; Eadie, M.J. and Tyrer, J.H.: Plasma protein binding of carbamazepine. Clinical Pharmacology and Therapeutics 17: 433–440 (1975).
Hooper, W.D.; Du Betz, D.K.; Eadie, M.J. and Tyrer, J.H.: Preliminary observations on the clinical pharmacology of carbamazepine (‘Tegretor’). Proceedings of the Australian Association of Neurologists 11: 189–198 (1974b).
Hooper, W.D.; Kunze, H.E. and Eadie, M.J.: Pharmacokinetics and bioavailability of methylphenobarbital in man. Therapeutic Drug Monitoring 3: 39–44 (1981).
Hooper, W.D.; Sutherland, J.M.; Bochner, F.; Tyrer, J.H. and Eadie, M.J.: The effect of certain drugs on the plasma protein binding of diphenylhydantoin. Australian and New Zealand Journal of Medicine 3: 377–381 (1973).
Hori, M.; Ito, T.; Yoshida, K. and Shimizu, M.: Effect of anti-convulsants on spiking activity induced by cortical freezing in cats. Epilepsia 20: 25–36 (1979).
Horning, M.G.; Brown, L.; Nowlin, J.; Lertratanangkoon, K.; Kellaway, P. and Zion, T.E.: Use of saliva in therapeutic drug monitoring. Clinical Chemistry 23: 157–164 (1977).
Horning, M.G.; Nowlin, J.; Butler, CM.; Lertratanangkoon, K.; Sommer, K. and Hill, R.M.: Clinical applications of gas chromatograph/mass spectrometer/computer systems. Clinical Chemistry 21: 1282–1287 (1975).
Houghton, G.W.; Richens, A.; Toseland, P.A.; Davidson, S. and Falconer, M.A.: Brain concentrations of phenytoin phenobarbitone and primidone in epileptic patients. European Journal of Clinical Pharmacology 9: 73–78 (1975).
Hunter, J.; Maxwell, J.D.; Stewart, D.A., Parsons, V. and Williams, R.: Altered calcium metabolism in epileptic children on anticonvulsants. British Medical Journal 4: 202–204 (1971).
Hvidberg, E.F. and Dam, M.: Clinical pharmacokinetics of anticonvulsants. Clinical Pharmacokinetics 1: 161–188 (1976).
Hvidberg, E.F. and Sjo, O.: Clinical pharmacokinetic experiences with clonazepam; in Schneider et al. (Eds) Clinical Pharmacology of Antiepileptic Drugs, pp. 242–246 (Springer, Berlin 1975).
Hyman, N.M.; Dennis, P.D. and Sinclair, K.G.A.: Tremor due to sodium valproate. Neurology 29: 1177–1180 (1979).
Iisalo, E.; Kangas, L. and Ruikka, I.: Pharmacokinetics of nitrazepam in young volunteers and aged patients. British Journal of Clinical Pharmacology 4: 646P-647P (1977).
Jacobi, G.; Thorbeck, R.; Ritz, A.; Janssen, W. and Schmidts, H.-L.: Fatal hepatotoxicity in child on phenobarbitone and sodium valproate. Lancet 1: 712–713 (1980).
Janz, D.: The teratogenic risk of antiepileptic drugs. Epilepsia 16: 159–169(1975).
Janz, D.; Bossi, L.; Dam, M.; Helge, H.; Richens, A. and Schmidt, D.: Epilepsy, pregnancy, and the child (Raven Press, New York 1982).
Jakobs, C. and Löscher, W.: Identification of metabolites of valproic acid in serum of humans, dog, rat and mouse. Epilepsia 19: 591–602 (1978).
Jensen, O.N. and Olesen, O.V.: Subnormal serum folate due to anticonvulsant therapy. A double blind study of the effect of folic acid treatment in patients with drug-induced subnormal serum folates. Archives of Neurology 22: 181–182 (1970).
Johannessen, S.I.: Antiepileptic drugs: Pharmacokinetic and clinical aspects. Therapeutic Drug Monitoring 3: 17–37 (1981).
Johannessen, S.I. and Strandjord, R.E.: The concentration of carbamazepine (Tegretol®) in serum and in cerebrospinal fluid in patients with epilepsy. Acta Neurologica Scandinavica 48 (Suppl. 51): 445–446 (1972).
Johannessen, S.I. and Strandjord, R.E.: Absorption and protein binding in serum of several anti-epileptic drugs; in Schneider et al. (Eds) Clinical Pharmacology of Antiepileptic Drugs, pp. 262–273 (Springer, Berlin 1975).
Johannessen, S.I.; Strandjord, R.E. and Munthekaas, A.W.: Lack of effect of clonazepam on serum levels of diphenylhydantoin, phenobarbital and carbamazepine. Acta Neurologica Scandinavica 55: 506–512 (1977).
Johnson, R.F.; Schenker, S.; Roberts, R.K.; Desmond, P.V. and Wilkinson, G.R.: Plasma binding of benzodiazepines in humans. Journal of Pharmacological Sciences 68: 1320–1322 (1979).
Jubiz, W.; Meikle, A.W.; Levinson, R.A.; Mizutani, S.; West, CD. and Tyler, F.H.: Effect of phenytoin (diphenylhydantoin) on the metabolism of dexamethasone. New England Journal of Medicine 283: 11–14(1970).
Jung, D.; Powell, J.R.; Watson, P. and Perrier, D.: Effect of dose on phenytoin absorption. Clinical Pharmacology and Therapeutics 28: 479–485 (1980).
Kallberg, N.; Agurell, S.; Ericcson, O.; Bucht, E.; Jailing, B. and Boreus, L.O.: Quantitation of phenobarbital and its main metabolites in human urine. European Journal of Clinical Pharmacology 9: 161–168 (1975).
Kaneko, S.; Sato, T. and Suzuki, K.: The level of anticonvulsants in breast milk. British Journal of Clinical Pharmacology 7: 624–627(1979).
Kangas, L. and Breimer, D.D.: Clinical pharmacokinetics of nitrazepam. Clinical Pharmacokinetics 6: 346–366 (1981).
Kangas, L.; Iisalo, E.; Kanto, J.; Lehtinen, V.; Pynnonen, S.; Ruikka, I.; Salminen, J.; Sillanpaa, M. and Syvalahti, E.: Human pharmacokinetics of nitrazepam: Effect of age and diseases. European Journal of Clinical Pharmacology 15: 163–170 (1979).
Kangas, L.; Kanto, J. and Erkkola, R.: Transfer of nitrazepam across the human placenta. European Journal of Clinical Pharmacology 12: 355–357 (1977a).
Kangas, L.; Kanto, J. and Surtola, T.: Cerebrospinal fluid concentrations and serum protein binding of diazepam and N-demethyldiazepam. Acta Pharmacologica et Toxicologica 35 (Suppl. 1): No. 48 (1974).
Kangas, I.; Kanto, J.; Surtola, T. and Pekkarinen, A.: Cerebrospinal-fluid concentrations of nitrazepam in man. Acta Pharmacologica et Toxicologica 41: 74–79 (1977b).
Kanto, J.H.; Pihlajamaki, K.K. and Iisalo, E.U.M.: Concentrations of diazepam in adipose tissue of children. British Journal of Anaesthesia 46: 168 (1974).
Kapetanovic, I.M.; Kupferberg, HJ.; Porter, R.J.; Theodore, W.; Schulman, E. and Penry, J.K.: Mechanism of valproate-phenobarbital interaction in epileptic patients. Clinical Pharmacology and Therapeutics 29: 480–486 (1981).
Kaplan, S.A.; Alexander, K.; Jack, M.L.; Puglisi, C.V.; de Silva, J.A.F.; Lee, T.L. and Weinfeld, R.E.: Pharmacokinetic profiles of clonazepam in dog and humans and of flunitrazepam in dog. Journal of Pharmaceutical Sciences 63: 527–532 (1974).
Kaplan, S.A.; Jack, M.L.; Alexander, K. and Weinfeld, R.E.: Pharmacokinetic profile of diazepam in man following single intravenous and oral and chronic oral administrations. Journal of Pharmaceutical Sciences 62: 1789–1796 (1973).
Kapur, R.N.; Girgis, S.; Little, T.M. and Masotti, R.E.: Diphenylhydantoin-induced gingival hyperplasia: Its relationship to dose and serum level. Developmental Medicine and Child Neurology 15: 483–487 (1973).
Karlin, J.M. and Kutt, H.: Acute diphenylhydantoin intoxication following halothane anesthesia. Journal of Pediatrics 76: 941–944 (1970).
Kater, R.M.H.; Roggin, G.; Tobon, F.; Zieve, P. and Iber, F.L.: Increased rate of clearance of drugs from the circulation of alcoholics. American Journal of the Medical Sciences 258: 35–39 (1969).
Kattan, K.R.: Thickening of the heel pad associated with long term Dilantin therapy. American Journal of Roentgenology 124: 52–56 (1975).
Kaufmann, R.E.; Habersang, R. and Lanksy, L.: Kinetics of primidone metabolism and excretion in children. Clinical Pharmacology and Therapeutics 22: 200–206 (1977).
Kendig, J.J.: Barbiturates: Active form and site of action at node of Ranvier sodium channels. Journal of Pharmacology and Experimental Therapeutics 218: 175–181 (1981).
Kiorboe, E.: Phenytoin intoxication during treatment with antabuse (disulfiram). Epilepsia 7: 246–249 (1966).
Klotz, U. and Antonin, K.H.: Pharmacokinetics and bioavailability of sodium valproate. Clinical Pharmacology and Therapeutics 21: 736–743 (1977).
Klotz, U.; Antonin, K.-H. and Bieck, P.R.: Pharmacokinetics and plasma binding of diazepam in man, dog, rabbit, guinea pig and rat. Journal of Pharmacology and Experimental Therapeutics 199: 67–73 (1976).
Klotz, U.; Antonin, K.H.; Brügel, H. and Bieck, P.R.: Disposition of diazepam and its major metabolite desmethyldiazepam in patients with liver disease. Clinical Pharmacology and Therapeutics 21: 430–436 (1977).
Klotz, U.; Avant, G.R.; Hoyumpa, A.; Schenker, S. and Wilkinson, G.R.: The effects of age and liver disease on the disposition and elimination of diazepam in adult man. Journal of Clinical Investigation 55: 347–359 (1975).
Knopp, R.H.; Sheinin, J.C. and Freinkel, N.: Diphenylhydantoin and an insulin secreting islet adenoma. Archives of Internal Medicine 130: 904–908 (1972).
Kostenbauder, H.B.; Rapp, R.P.; McGovren, J.P.; Foster, T.S.; Perrier, D.G.; Blacker, H.M.; Hulon, W.C. and Kinkel, A.W.: Bioavailability and single-dose pharmacokinetics of intramuscular phenytoin. Clinical Pharmacology and Therapeutics 18:449–456(1975).
Koup, J.R.; Gibaldi, M.; McNamara, P.; Hilligoss, D.M.; Colburn, W.A. and Bruck, E.: Interaction of chloramphenicol with phenytoin and phenobarbital. Case report. Clinical Pharmacology and Therapeutics 24: 571–575 (1978a).
Koup, J.R.; Rose, J.Q. and Cohen, M.E.: Ethosuximide pharmacokinetics in a pregnant patient and her newborn. Epilepsia 16: 535–539 (1978b).
Kristensen, M.; Hansen, J.M. and Skovsted, L.: The influence of phenobarbital on the half-life of diphenylhydantoin in man. Acta Medical Scandinavica 185: 347–350 (1969).
Kuhara, T. and Matsumoto, I.: Metabolism of branch medium chain length fatty acid. I-Omega oxidation of sodium dipropylacetate in rats. Biomedical Mass Spectrometry 1: 291–294 (1974).
Kuiper, J.J.: Lymphocytic thryoiditis possibly induced by diphenylhydantoin. Journal of the American Medical Association 210: 2370–2372 (1969).
Kunze, H.E.; Hooper, W.D. and Eadie, M.J.: The metabolism of methylphenobarbitone in man. Asian Journal of Clinical Sciences 1: 115–119(1980).
Kupferberg, HJ.; Jeffrey, W. and Hunninghake, D.B.: Effect of methylphenidate on plasma anticonvulsant level. Clinical Pharmacology and Therapeutics 13: 201–204 (1972).
Kutt, H.: Biochemical and genetic factors regulating Dilantin® metabolism in man. Annals of the New York Academy of Science 179: 704–722 (1971).
Kutt, H.: Interactions of antiepileptic drugs. Epilepsia 16: 393–402 (1975).
Kutt, H.; Haynes, M.; Verebely, K. and McDowell, F.: The effect of phenobarbital on plasma diphenylhydantoin level and metabolism in man and in rat liver microsomes. Neurology 19: 611–616(1969).
Kutt, H. and Louis, S.: Anticonvulsant drugs. II. Clinical pharmacological and therapeutics aspects. Drugs 4: 256–282 (1972).
Kutt, H. and McDowell, F.: Management of epilepsy with diphenylhydantoin sodium. Journal of the American Medical Association 203: 969–972 (1968).
Lambie, D.G. and Johnson, R.H.: The effect of phenytoin on phenobarbitone and primidone metabolism. Journal of Neurology, Neurosurgery and Psychiatry 44: 148–151 (19S1).
Lambie, D.G.; Nanda, R.N.; Johnson, R.H. and Shakir, R.A.: Therapeutic and pharmacokinetic effects of increasing phenytoin in chronic epileptics on multiple drug therapy. Lancet 7: 386–389(1976).
Lander, CM.; Eadie, M.J. and Tyrer, J.H.: Interactions between anticonvulsants. Proceedings of the Australian Association of Neurologists 12: 111–116 (1975).
Lander, CM.; Edwards, V.E.; Eadie, M.J. and Tyrer, J.H.: Plasma anticonvulsant concentrations during pregnancy. Neurology 27: 128–131 (1977).
Lander, CM.; Livingstone, I.; Tyrer, J.H. and Eadie, M.J.: The clearance of anticonvulsant drugs in pregnancy. Clinical and Experimental Neurology 17: 71–78 (1981).
Lascelles, P.T.; Kocen, R.S. and Reynolds, E.H.: The distribution of plasma phenytoin levels in epileptic patients. Journal of Neurology, Neurosurgery and Psychiatry 33: 501–505 (1970).
Levi, A.J.; Sherlock, S. and Walker, D.: Phenylbutazone and isoniazid metabolism in patients with liver disease in relation to previous drug therapy. Lancet 2: 1275–1279 (1968).
Levy, R.H. and Koch, K.M.: Drug interactions with valproic acid. Drugs 24: 543–556 (1982).
Linarelli, L.G.; Hengstenberg, F.H. and Drash, A.L.: Effect of phenobarbital on hyperlipemia in patients with intrahepatic and extrahepatic cholestasis. Journal of Pediatrics 83: 291–293 (1973).
Livingstone, S.: Comprehensive management of epilepsy in infancy, childhood and adolescence (Charles C. Thomas, Springfield 1972).
Louiseau, P.: Sodium valproate, platelet dysfunction and bleeding. Epilepsia 22: 141–146 (1981).
Löscher, W.: Serum protein binding and pharmacokinetics of valproate in man, dog, rat and mouse. Journal of Pharmacology and Experimental Therapeutics 204: 255–261 (1978).
Löscher, W.: A comparative study of the protein binding of anticonvulsant drugs in serum of dog and man. Journal of Pharmacology and Experimental Therapeutics 208: 429–435 (1979).
Löscher, W.: Concentration of metabolites of valproic acid in plasma of epileptic patients. Epilepsia 22: 169–178 (1981a).
Löscher, W.: Anticonvulsant activity of metabolites of valproic acid. Archives Internationales de Pharmacodynamie et de Therapie 249: 158–163 (1981b).
Louis, S.; Kutt, H. and McDowell, F.: Intravenous diphenylhydantoin in experimental seizures. II. Effect on penicillin-induced seizures in the cat. Archives of Neurology 18: 472–477 (1968).
Lous, P.: Elimination of barbiturates; in Johannsen (Ed.) Barbiturate Poisoning and Tenanus, pp. 341–350 (Little Brown, Boston 1966).
Lund, L.; Alvan, G.; Berlin, A. and Alexanderson, B.: Pharmacokinetics of single and multiple doses of phenytoin in man. European Journal of Clinical Pharmacology 7: 81–86 (1974).
Lund, L.; Berlin, A. and Lunde, P.K.M.: Plasma protein binding of diphenylhydantoin in patients with epilepsy. Agreement between the unbound fraction in plasma and the concentration in the cerebrospinal fluid. Clinical Pharmacology and Therapeutics 13: 196–200 (1972).
Lund, L.; Lunde, P.K.; Rane, A.; Borgå, O. and Sjöqvist, F.: Plasma protein binding, plasma concentrations, and effects of diphenylhydantoin in man. Annals of the New York Academy of Science 179: 723–728 (1971).
Lunde, P.K.M.; Rane, A.; Yaffe, S.J.; Lund, L. and Sjöqvist, F.: Plasma protein binding of diphenylhydantoin in man. Interaction with other drugs and the effect of temperature and plasma dilution. Clinical Pharmacology and Therapeutics 11: 846–855 (1970).
McAuliffe, J.J.; Sherwin, A.L.; Leppik, I.E.; Fayle, S.A. and Pippenger, C.E.: Salivary levels of anticonvulsants: A practical approach to drug monitoring. Neurology 27: 409–413 (1977).
MacKichan, J.J.; Duffner, P.K. and Cohen, M.E.: Salivary concentrations and plasma protein binding of carbamazepine and carbamazepine 10,11-epoxide in epileptic patients. British Journal of Clinical Pharmacology 12: 31–37 (1981).
Malherbe, C; Burrill, K.C.; Levin, S.R.; Karam, J.H. and Forsham, P.H.: Effect of diphenylhydantoin on insulin secretion in man. New England Journal of Medicine 286: 339–342 (1972).
Mandelli, M.; Tognoni, G. and Garattini, S.: Clinical pharmacokinetics of diazepam. Clinical Pharmacokinetics 3: 72–91 (1978).
Marcucci, C; Guaitani, A.; Kvetina, J.; Mussini, E. and Garattini, S.: Species difference in diazepam metabolism and anticonvulsant effect. European Journal of Pharmacology 4: 467–470 (1968).
Marescaux, C; Warter, J.M.; Micheletti, G.; Rumbach, L.; Coquillat, G. and Kurtz, D.: Stuporous episodes during treatment with sodium valproate: Report of seven cases. Epilepsia 23: 297–305 (1982).
Mark, L.C.: Metabolism of barbiturates in man. Clinical Pharmacology and Therapeutics 4: 504–530 (1963).
Marquis, J.-F.; Carruthers, S.G.; Spence, J.D.; Brownstone, Y.S. and Toogood, J.H.: Phenytoin-theophylline interaction. New England Journal of Medicine 307: 1189–1190 (1982).
Martin, E.; Tozer, T.N.; Sheiner, L.B. and Riegelman, S.: The clinical pharmacokinetics of phenytoin. Journal of Pharmacokinetics and Biopharmaceutics 5: 579–596 (1977).
Martin, P.R.; Kapur, B.M.; Whiteside, E.A. and Sellers, E.M.: Intravenous phenobarbital therapy in barbiturate and other hypnosedative withdrawal reactions: A kinetic approach. Clinical Pharmacology and Therapeutics 26: 256–264 (1979).
Mattson, R.H.; Gallagher, B.B.; Reynolds, E.H. and Glass, D.: Folate therapy in epilepsy. A controlled study. Archives of Neurology 29: 78–81 (1973).
Mawer, G.E.; Mullen, P.W.; Rodgers, M.; Robins, A.J. and Lucas, S.B.: Phenytoin dose adjustment in epileptic patients. British Journal of Clinical Pharmacology 1: 163–168 (1974).
Meberg, A.; Langslet, A.; Bredesen, J.E. and Lunde, P.K.M.: Plasma concentration of diazepam and N-desmethyldiazepam in children after a single rectal or intramuscular dose of diazepam. European Journal of Clinical Pharmacology 14: 273–276 (1978).
Meinardi, H.; Van Der Kleijn, E.; Meijer, J.W.A. and Van Rees, H.: Absorption and distribution of antiepileptic drugs. Epilepsia 16: 353–365 (1975).
Meldrum, B.S.: Mode of action of anticonvulsant drugs: Biochemical effects; in Tyrer (Ed.) The Treatment of Epilepsy, pp. 29–59 (P Press, Lancaster 1980
Meyer, J.G.: The teratological effect of anticonvulsants and the effects of pregnancy and birth. European Neurology 10: 179–190 (1973).
Millichap, J.G. and Ortiz, W.R.: Nitrazepam in myoclonic epilepsies. American Journal of Disease in Childhood 112: 242–248 (1966).
Mirkin, B.L.: Diphenylhydantoin: Placental transport, fetal localization, neonatal metabolism and possible teratogenic effects. Journal of Pediatrics 78: 329–337 (1971).
Mirkin, B.L. and Wright, F.: Drug interactions: Effect of methylphenidate on the disposition of diphenylhydantoin in man. Neurology 21: 1123–1128 (1971).
Monaco, F.; Piredda, S.; Mastropaolo, C.; Tondi, M. and Mutani, R.: Diphenylhydantoin and primidone in tears. Epilepsia 22: 185–188(1981).
Monk, A. and Richens, A.: Effect of a single dose of sodium valproate on serum phenytoin concentration and protein binding in epileptic patients. Clinical Pharmacology and Therapeutics 27: 89–95 (1980).
Morselli, P.L.: Carbamazepine: Absorption, distribution and excretion; in Penry (Ed.) Advances in Neurology, Vol. 12 (Raven Press, New York 1975).
Morselli, P.L.; Bossi, L. and Gerna, M.: Pharmacokinetic studies with carbamazepine in epileptic patients; in Birkmayer (Ed.) International Symposium on Epileptic Seizures — Behaviour — Pain, pp. 141–150 (Huber, Berne 1975a).
Morselli, P.L.; Gerna, M.; De Maio, D.; Zanda, G.; Viani, F. and Garattini, S.: Pharmacokinetic studies on carbamazepine in volunteers and in epileptic patients; in Schneider et al. (Eds) Clinical Pharmacology of Antiepileptic Drugs, pp. 166–179 (Springer, Berlin 1975b).
Morselli, P.L.; Mandelli, M.; Tognoni, G.; Principi, N.; Pardi, G. and Sereni, F.: Drug interaction in the human fetus and in the newborn infant; in Morselli et al. (Eds) Drug Interactions, pp. 259–270 (Raven Press, New York 1974).
Mosekilde, L. and Meisen, F.: Anticonvulsant osteomalacia determined by quantitative analysis of bone changes: Population study and possible risk factors. Acta Medica Scandinavica 199: 349–355 (1976).
Muller, W. and Wollen, U.: Characterization of the binding of benzodiazepines to human serum albumin. Naunyn-Schmie-deberg’s Archives of Pharmacology 280: 229–237 (1973).
Nanda, R.N.; Johnson, R.H.; Keogh, HJ.; Lambie, D.G. and Melville, I.D.: Treatment of epilepsy with clonazepam and its effect on other anticonvulsants. Journal of Neurology, Neurosurgery and Psychiatry 40: 538–543 (1977).
Nau, H.; Kuhnz, W.; Egger, H.-J.; Rating, D. and Helge, H.: Anti-convulsants during pregnancy and lactation: Transplacental, maternal and neonatal pharmacokinetics. Clinical Pharmacokinetics 7: 508–543 (1982).
Neuvonen, P.J. and Penttilä, O.: Interaction between doxycycline and barbiturates. British Medical Journal 1: 535–536 (1974).
Neuvonen, P.J.; Penttilä, O.; Lentovarra, R. and Aho, K.: Effect of antiepileptic drugs on the elimination of various tetracycline derivatives. European Journal of Clinical Pharmacology 9: 147–154(1975).
Neuvonen, P.J.; Tokola, R.A. and Kaste, M.: Cimetidine-phenytoin interaction: Effect on serum phenytoin concentration and antipyrine test. European Journal of Clinical Pharmacology 21:215–220(1981).
Nitsche, V. and Mascher, H.: The pharmacokinetics of valproic acid after oral and parenteral administration in healthy volunteers. Epilepsia 23: 153–162 (1982).
Olesen, O.V.: Disulfiramum (Antabuse) as inhibitor of phenytoin metabolism. Acta Pharmacologica et Toxicologica 24: 317–322 (1966).
Olesen, O.V. and Jensen, O.N.: Drug-interaction between sulthiame (Ospolot®) and phenytoin in the treatment of epilepsy. Danish Medical Bulletin 16: 154–158 (1969).
Olesen, O.V. and Jensen, O.N.: The influence of folic acid on phenytoin (DPH) metabolism and the 24 hours fluctuation in urinary output of 5-(p-hydroxyphenyl)-5 phenyl-hydantoin (HPPH). Acta Pharmacologica et Toxicologica 28: 265–269 (1970).
Olsen, G.D.; Bennett, W.M. and Porter, G.A.: Morphine and phenytoin binding to plasma proteins in renal and hepatic failure. Clinical Pharmacology and Therapeutics 17: 677–684 (1975).
Orr, J.M.; Abbott, F.S.; Farrell, K.; Ferguson, S.; Sheppard, I. and Godolphin, W.: Interaction between valproic acid and aspirin in epileptic children: Serum protein binding and metabolic effects. Clinical Pharmacology and Therapeutics 31: 642–649 (1982).
Ostrovskaya, R.U. and Molodavkin, G.M.: The GABAergic mechanism of the effects of diazepam on cortical neurons. Bulletin of Experimental Biology and Medicine 82: 1343–1346 (1977).
Painter, M.J.; Pippinger, C; Carter, G. and Pitlick, W.: Metabolism of phenobarbital and phenytoin by neonates with seizures. Neurology 27: 370 (1977).
Parker, W.A. and Shearer, C.A.: Phenytoin hepatoxicity: A case report and review. Neurology 29: 175–178 (1979).
Parnas, J.; Flachs, H.; Gram, L. and Würtz-Jorgensen, A.: Excretion of antiepileptic drugs in sweat. Acta Neurologica Scandinavica 58: 197–204 (1978).
Patel, I.H. and Levy, R.H.: Valproic acid binding to human serum albumin and determination of free fraction in the presence of anticonvulsant and free fatty acids. Epilepsia 20: 85–90 (1979).
Patel, I.H.; Levy, R.H. and Cutler, R.E.: Phenobarbital-valproic acid interaction in normal man. Clinical Pharmacology and Therapeutics 25: 241 (1979).
Patel, I.H.; Levy, R.H. and Cutler, R.E.: Phenobarbital-valproic acid interaction. Clinical Pharmacology and Therapeutics 27: 515–521 (1980).
Patsalos. P.N. and Lascelles, P.T.: Changes in regional brain levels of amino acid putative neurotransmitters after prolonged treatment with the anticonvulsant drugs diphenylhydantoin, phenobarbitone, sodium valproate, ethosuximide and sulthiame in the rat. Journal of Neurochemistry 36: 688–695 (1981).
Patterson, M.; Heazlewood, R.; Smithurst, B. and Eadie, M.J.: Plasma protein binding of phenytoin in the aged: In vivo studies. British Journal of Clinical Pharmacology 13: 423–425 (1982).
Paxton, J.W. and Donald, R.A.: Concentrations and kinetics of carbamazepine in whole saliva, parotid saliva, serum ultrafiltrate, and serum. Clinical Pharmacology and Therapeutics 28: 695–702 (1980).
Paxton, J.W.; Rowell, F.J.; Ratcliffe, J.G.; Lambie, D.G.; Nanda, R.; Melville, I.D. and Johnson, R.H.: Salivary phenytoin radioimmunoassay. A simple method for the assessment of non-protein bound drug concentrations. European Journal of Clinical Pharmacology 11: 71–74 (1977).
Penttilä, O.; Neuvonen, P.J.; Aho, K. and Lentovarra, R.: Interaction between doxycycline and some antiepileptic drugs. British Medical Journal 2: 470–472 (1974).
Perucca, E.: Plasma protein binding of phenytoin in health and disease: Relevance to therapeutic drug monitoring. Therapeutic Drug Monitoring 2: 331–344 (1980).
Perucca, E.: Pharmacokinetic interactions with antiepileptic drugs. Clinical Pharmacokinetics 7: 57–84 (1982).
Perucca, E.: Free level monitoring of antiepileptic drugs. Clinical usefulness and case studies. Clinical Pharmacokinetics 9 (Suppl. 1): 71–78 (1984).
Perucca, E.; Gatti, G.; Frigo, G.M. and Crema, A.: Pharmacokinetics of valproic acid after oral and intravenous administration. British Journal of Clinical Pharmacology 5: 313–318 (1978).
Perucca, E.; Hebdige, S.; Frigo, G.M.; Gatti, G.; Lecchini, S. and Crema, A.: Interaction between phenytoin and valproic acid: Plasma protein binding and metabolic effects. Clinical Pharmacology and Therapeutics 28: 779–789 (1980).
Perucca, E. and Richens, A.: Interaction between phenytoin and imipramine. British Journal of Clinical Pharmacology 4: 485–486 (1977).
Perucca, E. and Richens, A.: Reduction of oral bioavailability of lignocaine by induction of first pass metabolism in epileptic patients. British Journal of Clinical Pharmacology 8: 21–31 (1979).
Perucca, E. and Richens, A.: Anticonvulsant drug interactions; in Tyrer, J.H. (Ed.) The Treatment of Epilepsy, pp. 95–128 (MTP Press, Lancaster 1980).
Perucca, E.; Richens, A. and Ruprah, M.: Serum protein binding of phenytoin in pregnant women. British Journal of Clinical Pharmacology 11: 409P-410P (1981a).
Perucca, E.; Ruprah, M. and Richens, A.: Decreased serum protein binding of diazepam and valproic acid in pregnant women. British Journal of Clinical Pharmacology 12: 276P (1981b).
Petereit, L.B. and Meikle, A.W.: Effectiveness of prednisolone during phenytoin therapy. Clinical Pharmacology and Therapeutics 22: 912–916 (1977).
Pieri, L. and Haefely, W.: The effect of diphenylhydantoin, diazepam and clonazepam on the activity of Purkinje cells in the rat cerebellum. Naunyn-Schmiedeberg’s Archives of Pharmacology 296: 1–4 (1976).
Piredda, S. and Monaco, F.: Ethosuximide in tears, saliva, and cerebrospinal fluid. Therapeutic Drug Monitoring 3: 321–323 (1981).
Pitlick, W.H.; Levy, R.H.; Troupin, A.S. and Green, J.R.: Pharmacokinetic model to describe self-induced decreases in steady-state concentrations of carbamazepine. Journal of Pharmaceutical Sciences 65: 462–463 (1976).
Plaa, G.L.: Acute toxicity of antiepileptic drugs. Epilepsia 16: 183–191 (1975).
Pond, S. and Kretschzmar, K.M.: Effect of phenytoin on meperidine clearance and normeperidine formation. Clinical Pharmacology and Therapeutics 30: 680–686 (1981).
Pugh, R.N.H.; Geddes, A.M. and Yeoman, W.B.: Interaction of phenytoin with chlorpheniramine. British Journal of Clinical Pharmacology 2: 173–175(1975).
Pynnönen, S.: Pharmacokinetics of carbamazepme in man: A review. Therapeutic Drug Monitoring 1: 409–431 (1979).
Pynnönen, S. and Sillanpaa, M.: Carbamazepine and mother’s milk. Lancet 3: 563 (1975).
Pynnönen, S.; Sillanpaa, M.; Frey, H. and Iisalo, E.: Carbamazepine and its 10,11-epoxide in children and adults with epilepsy. Europ. J. Clin. Pharmacol. 11: 129–133 (1977).
Rambeck, B.: Pharmacological interactions of methsuximide with phenobarbital and phenytoin in hospitalised epileptic patients. Epilepsia 20: 147–156 (1979).
Randall, L.O.; Schallek, W.; Scheckel, C; Bagdon, R.E. and Rieder, J.: Zur Pharmakologie von Mogadon einem Schlafmittel mit neuartigem Wirkungsmechanismus. Schweizerische Medizinische Wochenschrifte 95: 334–337 (1965).
Rane, A.; Garle, M.; Borgå, O. and Sjöqvist, F.: Plasma disappearance of transplacentally transferred diphenylhydantoin in the newborn studied by mass fragmentography. Clinical Pharmacology and Therapeutics 15: 39–45 (1974).
Rane, A.; Lunde, P.K.M.; Jailing, B.; Yaffe, S.J. and Sjöqvist, F.: Plasma protein binding of diphenylhydantoin in normal and hyperbilirubinemic infants. Journal of Pediatrics 78: 877–882 (1971).
Rausing, A. and Trell, E.: Malignant lymphogranulomatosis and anticonvulsant therapy. Acta Medica Scandinavica 189: 131–136 (1971).
Rawlins, M.D.; Couste, P.; Bertilsson, L. and Palmér, L.: Distribution and elimination kinetics of carbamazepine in man. European Journal of Clinical Pharmacology 8: 91–96 (1975).
Redenbaugh, J.E.; Sato, S.; Penry, J.K.; Dreifuss, F.E. and Kupferberg, H.J.: Sodium valproate: Pharmacokinetics and effectiveness in treating intractable seizures. Neurology 30: 1–6 (1980).
Reinken, L: Die Wirkung von Hydantoin und Succinimid auf den Vitamin B6 Stoffwechsel. Clinica Chimica Acta 48: 435–436 (1973).
Reynolds, E.H.: Chronic antiepileptic toxicity: A review. Epilepsia 16: 319–352 (1975).
Reynolds, E.H.: Folate and epilepsy; in Bradford and Marsden (Eds) Biochemistry and Neurology, pp. 247–252 (Academic Press, London 1976).
Reynolds, E.H.; Fenton, G.; Fenwick, P.; Johnson, A.L. and Laundy, M.: Interaction of phenytoin and primidone. British Medical Journal 2: 594–595 (1975).
Reynolds, E.H. and Shor von, S.D.: Monotherapy or polytherapy for epilepsy? Epilepsia 22: 1–10 (1981).
Richens, A.: In discussion; in Schneider et al. (Eds) Clinical Pharmacology of Antiepileptic Drugs, pp. 46–47 (Springer, Berlin 1975).
Richens, A.: Drug treatment of epilepsy (Heinemann Medical Books, London 1976).
Richens, A.: Interactions with antiepileptic drugs. Drugs 13: 266–275 (1977).
Richens, A.: Clinical pharmacokinetics of phenytoin. Clinical Pharmacokinetics 4: 153–169 (1979).
Richens, A. and Houghton, G.W.: Effect of drug therapy on the metabolism of phenytoin; in Schneider et al. (Eds) Clinical Pharmacology of Antiepileptic Drugs, pp. 87–95 (Springer, Berlin 1975).
Richens, A.; Scoular,.T.; IAhmad, S. and Jordan, B.J.: Pharmacokinetics and efficacy of Epilim in patients receiving long-term therapy with other anticonvulsants; in Legg (Ed.) Clinical and Pharmacological Aspects of Sodium Valproate (Epilim) in the Treatment of Epilepsy, pp. 78–88 (MCS Consultants, Tunbridge Wells 1976).
Rieder, J. and Wendt, G.: Pharmacokinetics and metabolism of the hypnotic nitrazepam. Symposium on Benzodiazepines, Milan, Nov. 1–4, 1971 (Communication from Roche Products Ltd, 1971).
Rizzo, M.; Morselli, P.L. and Garattini, S.: Further observations on the interactions between phenobarbital and diphenylhydantoin during chronic treatment in the rat. Biochemical Pharmacology 21: 449–454 (1972).
Robert, E.: Valproic acid in pregnancy — association with spina bifida: A preliminary report. Clinical Pediatrics 22: 336 (1983).
Rogers, H.J.; Haslam, R.A.; Longstreth, J. and Lietman, P.S.: Phenytoin intoxication during concurrent diazepam therapy. Journal of Neurology, Neurosurgery and Psychiatry 40: 890–895 (1977).
Rothermich, N.O.: Diphenylhydantoin intoxication. Lancet 2: 640 (1966).
Ruprah, M.; Perucca, E. and Richens, A.: Decreased serum protein binding of phenytoin in late pregnancy. Lancet 2: 316–317 (1980).
Sackellares, J.C.; Lee, S.I. and Dreifuss, F.E.: Stupor following administration of valproic acid to patients receiving other antiepileptic drugs. Epilepsia 20: 697–703 (1979).
Sackellares, J.C.; Sato, S.; Dreifuss, F.E. and Penry, J.K.: Reduction of steady-state valproate levels by other antiepileptic drugs. Epilepsia 22: 437–441 (1981).
Saltzstein, S.L. and Ackerman, L.V.: Lymphadenopathy induced by anticonvulsant drugs and mimicking clinically and pathologically malignant lymphomas. Cancer 12: 164–182 (1959).
Sano, J.; Kawada, H.; Yamaguchi, N.; Kawakita, M. and Kobayashi, K.: Effects of phenytoin on serum γ-glutamyl transpeptidase activity. Epilepsia 22: 331–338 (1981).
Saxén, I. and Saxén, L.: Association between maternal intake of diazepam and oral clefts. Lancet 3: 498 (1975).
Schallek, W. and Kuehn, A.: Effects of trimethadione, diphenylhydantoin and chlordiazepoxide on after-discharges in brain of cat. Proceedings of the Society for Experimental Biology (New York 112: 813–817 (1963).
Schmidt, D. and Kupferberg, H.J.: Diphenylhydantoin, phenobarbital and primidone in saliva, plasma and cerebrospinal fluid. Epilepsia 16: 735–741 (1975).
Schneider, H.: Carbamazepine: The influence of other anti-epileptic drugs on its serum level; in Schneider et al. (Eds) Clinical Pharmacology of Antiepileptic Drugs, pp. 189–195 (Springer, Berlin 1975).
Schobben, A.F.A.M.: Pharmacokinetics and therapeutics in epilepsy (Stichting Studentenpers, Nijmegen 1979).
Schobben, E.; Van Der Kleijn, E. and Gabreels, F.J.M.: Pharmacokinetics of di-n-propylacetate in epileptic patients. European Journal of Clinical Pharmacology 8: 97–105 (1975).
Sellman, R.; Kanto, J.; Raijola, E. and Pekkarinen, A.: Induction effect of diazepam on its own metabolism. Acta Pharmacologica et Toxicologica 37: 345–351 (1975).
Serrano, E.E. and Wilder, B.J.: Intramuscular administration of diphenylhydantoin. Histologic follow-up study. Archives of Neurology 31: 276–278 (1974).
Shapiro, S.; Hartz, S.C.; Siskind, V.; Mitchell, A.C.; Slone, D.; Rosenberg, L.; Monson, R.R.; Heinonen, O.P.; Idanpaan-Heikkila, J.; Haro, S. and Saxén, L.: Anticonvulsants and parental epilepsy in the development of birth defects. Lancet 1: 272–275 (1976).
Sherwin, A.L.; Loynd, J.S.; Bock, G.W. and Sokolowski, CD.: Effect of age, sex, obesity and pregnancy on plasma diphenylhydantoin levels. Epilepsia 15: 507–521 (1974).
Sherwin, A.L. and Robb, J.P.: Ethosuximide: Relation of plasma level to clinical control; in Woodbury et al. (Eds) Antiepileptic Drugs, pp. 443–448 (Raven Press, New York 1972).
Shor von, S.D. and Reynolds, E.H.: Anticonvulsant peripheral neuropathy: A clinical and electrophysical study of patients on single drug treatment with phenytoin, carbamazepine or barbiturates. Journal of Neurology, Neurosurgery and Psychiatry 45: 620–626(1982).
Sjo, O.; Hvidberg, E.F.; Naestoft, J. and Lund, M.: Pharmacokinetics and side-effects of clonazepam and its 7-aminometabolite in man. European Journal of Clinical Pharmacology 8: 249–254(1975).
Skovsted, L.; Hansen, J.M.; Kristensen, M. and Christensen, L.K.: Inhibition of drug metabolism in man; in Morselli et al. (Eds) Drug Interactions, pp. 81–90 (Raven Press, New York 1974).
Slater, G.E. and Johnston, D.: Sodium valproate increases potassium conductance in Aplysia neurons. Epilepsia 19: 379–384 (1978).
Smith, G.A.; McKauge, L.; Du Betz, D.K.; Tyrer, J.H. and Eadie, M.J.: Factors influencing plasma concentrations of ethosuximide. Clinical Pharmacokinetics 4: 38–52 (1979).
So, E.L. and Penry, J.K.: Adverse effects of phenytoin on peripheral nerves and neuromuscular junction: A review. Epilepsia 22: 467–473 (1981).
Solomon, G.E.; Hilgartner, M.W. and Kutt, H.: Coagulation defects caused by diphenylhydantoin. Neurology 22: 1165–1171 (1972).
Solomon, H.M.; Reich, S.; Spirt, N. and Abrams, W.B.: Interactions between digitoxin and other drugs in vitro and in vivo. Annals of the New York Academy of Science 79: 362–369 (1971).
Somogyi, A.; Thielscher, S. and Gugler, R.: Influence of phenobarbital treatment on cimetidine kinetics. European Journal of Clinical Pharmacology 19: 343–347 (1981).
Spero, L.: Epilepsy. Lancet 2: 1319–1322 (1982).
Stephens, W.P.; Espir, M.L.E.; Tattersall, R.B.; Quinn, N.P.; Gladwell, S.R.F.; Galbraith, A.W. and Reynolds, E.H.: Water intoxication due to carbamazepine. British Medical Journal 1: 754–755 (1977).
Strandjord, R.E.; Johanessen, S.I. and Aarli, J.A.: Serum concentrations of immunoglobulins in patients with epilepsy treated with carbamazepine. Acta Neurologica Scandinavica 61: 260–263 (1980).
Suchy, F.J.; Balistrieri, W.F.; Buchino, J.J.; Sondheimer, J.M.; Bates, S.R.; Kearns, G.L.; Stull, J.D. and Bove, K.E.: Acute hepatic failure associated with the use of sodium valproate. New England Journal of Medicine 300: 962–966 (1979).
Sutton, G. and Kupferberg, HJ.: Isoniazid as an inhibitor of primidone metabolism. Neurology 25: 1179–1181 (1975).
Swanson, B.N.; Harland, R.C.; Dickinson, R.G. and Gerber, N.: Excretion of valproic acid into semen of rabbits and man. Epilepsia 19: 541–546 (1978).
Syversen, G.B.; Morgan, J.P.; Weintraub, M. and Myers, J.: Acetazolamide, induced interference with primidone absorption: Case reports and metabolic studies. Archives of Neurology 34: 80–84(1977).
Takeda, A.; Goto, H.; Amano, Y. and Kukino, K.: A study on serum and cerebrospinal fluid levels of sodium valproate (DPA), a new antiepileptic drug. Brain Development 8: 401–408 (1976).
Tang, B.K.; Kalow, W. and Grey, A.A.: Metabolic fate of phenobarbital in man. N-glucoside formation. Drug Metabolism and Disposition 7: 315–318 (1979).
Taylor, J.D.; Krahn, P.M. and Higgins, T.N.: Serum copper levels and diphenylhydantoin. American Journal of Clinical Pathology 61: 577–578 (1974).
Thiessen, J.J.; Sellers, E.M.; Denbeigh, P. and Dolman, I.: Plasma protein binding of diazepam and tolbutamide in chronic alcoholics. Journal of Clinical Pharmacology 16: 345–351 (1976).
Thompson, R.H.P.; Eddleston, A.L.W.F. and Williams, R.: Low plasma-bilirubin in epileptics on phenobarbitone. Lancet 1: 21–22 (1969).
Travers, R.D.; Reynolds, E.H. and Gallagher, B.B.: Variation in response to anticonvulsants in a group of epileptic patients. Archives of Neurology 27: 29–33 (1972).
Troupin, A.S. and Friel, P.: Anticonvulsant levels in saliva, serum and cerebrospinal fluid. Epilepsia 16: 223–227 (1975).
Troupin, A.S. and Ojemann, L.M.: Paradoxical intoxication — a complication of anticonvulsant intoxication. Epilepsia 16: 753–758 (1976).
Tyrer, J.H.; Eadie, M.J.; Sutherland, J.M. and Hooper, W.D.: An outbreak of anticonvulsant intoxication in an Australian city. British Medical Journal 4: 271–273 (1970).
Vajda, F.J.E.; Donnan, G.A.; Phillips, J. and Bladin, P.F.: Human brain, plasma and cerebrospinal fluid concentrations of sodium valproate after 72 hours of therapy. Neurology 31: 486–487 (1981).
Vajda, F.J.E.; Mihaly, G.W.; Miles, J.L.; Donnan, G.A. and Bladin, P.F.: Rectal administration of sodium valproate in status epilepticus. Neurology 28: 897–899 (1978).
Vajda, F.; Morris, P.; Drummer, O. and Bladin, P.: Studies on sodium valproate — a new anticonvulsant; in Legg (Ed.) Clinical and Pharmacological Aspects of Sodium Valproate (Epilim) in the Treatment of Epilepsy, pp. 92–100 (MCS Consultants, Tunbridge Wells 1976).
Vajda, F.J.E.; Prineas, R.J. and Lovell, R.R.H.: Interaction between phenytoin and benzodiazepines. British Medical Journal 1: 346 (1971).
Vajda, F.; Williams, F.M.; Davidson, S.; Falconer, M.A. and Breckenridge, A.: Human brain, cerebrospinal fluid, and plasma concentrations of diphenylhydantoin and phenobarbital. Clin. Pharmacol. Therap. 15: 597–603 (1974).
Vakil, S.D.; Critchley, E.M.R.; Philips, J.C.; Fahim, Y.; Haydock, C.; Cocks, A. and Dyer, T.: The effect of sodium valproate (Epilim) on phenytoin and phenobarbitone blood levels; in Legg (Ed.) Clinical and Pharmacological Aspects of Sodium Valproate (Epilim) in the Treatment of Epilepsy, pp. 75–77 (MCS Consultants, Tunbridge Wells 1976).
Valsalan, V.C. and Cooper, G.L.: Carbamazepine intoxication caused by interaction with isoniazid. British Medical Journal 285: 261–262 (1982).
Van der Kleijn, E.; Guelen, P.J.M.; Van Wijk, C. and Baars, I.: Clinical pharmacokinetics in monitoring chronic medication with anti-epileptic drugs; in Schneider et al. (Eds) Clinical Pharmacology of Antiepileptic Drugs, pp. 11–33 (Springer, Berlin 1975).
Van der KJeijn, E.; van Rossum, J.M.; Muskens, E.T.J.M. and Rijntjes, N.V.M.: Pharmacokinetics of diazepam in dogs, mice and humans. Acta Pharmacologica et Toxicologica 29 (Suppl. 3): 109–127 (1971).
Victor, A.; Lundberg, P.O. and Johansson, E.D.B.: Induction of sex hormone binding globulin by phenytoin. British Medical Journal 2: 934–935(1977).
Vida, J.A. (Ed.): Anticonvulsants (Academic Press, New York 1977).
Viswanathan, C.T.; Booker, H.E. and Welling, P.G.: Pharmacokinetics of phenobarbital following single and repeated doses. Journal of Clinical Pharmacology 19: 282–289 (1979).
Viukari, N.M.A. and Aho, K.: Digoxin-phenytoin interaction. British Medical Journal 2: 51 (1970).
Warren Jr, J.W., Bennaman, J.D.; Wannamaker, B.B. and Levy, R.H.: Kinetics of a carbamazepine-ethosuximide interaction. Clinical Pharmacology and Therapeutics 28: 646–651 (1980).
Warter, J.M.; Brandt, Ch.; Marescaux, Ch.; Rumbach, L.; Micheletti, G.; Chabrier, G.; Krieger, J. and Imler, M.: The renal origin of sodium valproate-induced hyperammonemia in fasting humans. Neurology 33: 1136–1140 (1983).
Wechselberg, K. and Hubel, G.: Zur Resorption und Verteilung von Methyl-Althyl-Succinimid (MAS) im Serum und Liquor bei kindern. Zeitschrift für Kinderheilkunde 100: 10–19 (1967).
Weedon, A.P.: Diphenylhydantoin sensitivity. A syndrome resembling infectious mononucleosis with a morbilliform rash and cholestatic hepatitis. Australian and New Zealand Journal of Medicine 5: 561–563 (1975).
Weisman, Y.; Fattal, A.; Eisenberg, Z.; Harel, S.; Spirer, Z. and Harell, A.: Decreased serum 24,25-dihydroxy vitamin D concentrations in children receiving chronic anticonvulsant therapy. British Medical Journal 2: 521–523 (1979).
Welton, D.G.: Exfoliated dermatitis and hepatitis due to phenobarbital. Journal of the American Medical Association 143: 232–234 (1950).
Westenberg, H.G.M.; Van Der Kleijn, E.; Oei, T.T. and De Zeeuw, R.A.: Kinetics of carbamazepine and carbamazepine-epoxide, determined by use of plasma and saliva. Clinical Pharmacology and Therapeutics 23: 320–328 (1978).
Whyte, M.P. and Dekaban, A.S.: Metabolic fate of phenobarbital. A quantitative study of p-hydroxy-phenobarbital elimination in man. Drug Metabolism and Distribution 5: 63–70 (1977).
Wilensky, A.J.; Friel, P.N.; Levy, R.H.; Comfort, C.P. and Kaluzny, S.P.: Kinetics of phenobarbital in normal subjects and epileptic patients. European Journal of Clinical Pharmacology 23: 87–92 (1982).
Williams, L.H.P.; Reynolds, R.P. and Emery, J.L.: Pancreatitis during sodium valproate treatment. Archives of Disease in Childhood 58: 543–544 (1983).
Windorfer Jr, A. and Pringsheim, W.: Studies on the concentrations of chloramphenicol in the serum and cerebrospinal fluid of neonates, infants and small children. Reciprocal reactions between chloramphenicol, penicillin and phenobarbitone. European Journal of Pediatrics 124: 129–138 (1977).
Windorfer Jr, A. and Sauer, W.: Drug interactions during anticonvulsant therapy in childhood: Diphenylhydantoin, primidone, phenobarbitone, clonazepam, nitrazepam, carbamazepine and dipropylacetate. Neuropaediatrie 8: 29–41 (1977).
Windorfer, A.; Sauer, W. and Gaedeke, R.: Elevation of diphenylhydantoin and primidone serum concentrations by addition of dipropylacetate, a new anticonvulsant drug. Acta Paediatrica Scandinavica 64: 771–772 (1975).
Woodbury, D.M. and Esplin, D.W.: Neuropharmacology and neurochemistry of anticonvulsant drugs. Proceedings of the Association for Research in Nervous and Mental Diseases 37: 24–56 (1959).
Woodbury, D.M.; Penry, J.K. and Pippenger, C.E. (Eds): Antiepileptic Drugs, 2nd ed. (Raven Press, New York 1982).
Wright. J.M.: Stokes, E.F. and Sweeney, V.P.: Isoniazid-induced carbamazepine toxicity and vice versa. New England Journal of Medicine 307: 1325–1327 (1982).
Yabuki, S. and Nakaya, K.: Immunoglobulin abnormalities in epileptic patients treated with diphenylhydantoin. Folia Psychiatrica Neurologica Japonica 30: 93–109 (1976).
Zafrani, E.S. and Berthelot, P.: Sodium valproate in the induction of unusual hepatotoxicity. Hepatology 2: 648–649 (1982).
Zimmerman, H.J. and Ishak, K.G.: Valproate-induced hepatic injury: Analyses of 23 fatal cases. Hepatology 2: 591–597 (1982).
Zimmerman, C.L.; Patel, I.H.; Levy, R.H.; Edwards, D.; Nelson, S.D. and Hutchinson, U.: Protein binding of valproic acid in the presence of elevated free fatty acids in patient and normal human serum. Epilepsia 21: 11–17 (1981).
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Eadie, M.J. Anticonvulsant Drugs. Drugs 27, 328–363 (1984). https://doi.org/10.2165/00003495-198427040-00003
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DOI: https://doi.org/10.2165/00003495-198427040-00003