Clinical Pharmacokinetics

, Volume 1, Issue 1, pp 52–66 | Cite as

Plasma Level Monitoring of Anticonvulsants

  • M. J. Eadie
Article

Summary

The plasma concentrations of anticonvulsant drugs, and of certain of their biologically active metabolites, tend to be proportionate to the antiepileptic effects of these drugs. Consequently, anticonvulsant drug levels in plasma are monitored to help guide the clinician in managing his patients’ epilepsies. In making use of the measurements, the clinician needs to know the relation between plasma level and biological effect for the various drugs. He also needs to have some awareness of simple pharmacokinetic principles. These are important in deciding when plasma levels should be monitored in relation to the patients’ clinical state, to the dosage interval, and to change in the dosage of anticonvulsant or other drug.

The clinician also requires pharmacokinetic knowledge in altering anticonvulsant drug dosage in his patients, and in interpreting plasma anticonvulsant level data, particularly when the patient is concurrently suffering from non-neurological disease. The ability to monitor plasma anticonvulsant levels has appreciably improved the treatment of epilepsy, but to obtain maximum benefits from the method, both pharmacokinetic insight and clinical wisdom are required.

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References

  1. Agurell, S.; Berlin, A.; Ferngren, H. and Hellstrom, B.: Plasma levels of diazepam after parenteral and rectal administration in children. Epilepsia (Amsterdam) 16: 277–283 (1975).CrossRefGoogle Scholar
  2. Albert, K.S.; Hallmark, M.R.; Carroll, M.E. and Wagner, J.G.: Quantitative separation of diphenylhydantoin and its para-hydroxylated metabolites by high-performance liquid chromatography. Research Communications in Chemical Pathology and Pharmacology 6: 845–854 (1973).PubMedGoogle Scholar
  3. Arnold, K. and Gerber, N.: The rate of decline of diphenylhydantoin in human plasma. Clinical Pharmacology and Therapeutics 11: 121–134 (1970).PubMedGoogle Scholar
  4. Atkinson, A.J. and Shaw, J.M.: Pharmacokinetic study of a patient with diphenylhydantoin toxicity. Clinical Pharmacology and Therapeutics 14: 521–528 (1973).PubMedGoogle Scholar
  5. Atwell, S.H.; Green, V.A. and Harvey, W.G.: Development and evaluation of method for simultaneous determination of phenobarbital and diphenylhydantoin in plasma by high-pressure liquid chromatography. Journal of Pharmaceutical Sciences 64: 806–809 (1975).PubMedCrossRefGoogle Scholar
  6. Barron, S.J.; Darcey, B.A. and Booker, H.E.: Metabolism and kinetics of methsuximide in man. Neurology (Minneapolis) 24: 386 (1974).Google Scholar
  7. Baumel, LP.; Gallagher, B.B. and Mattson, R.H.: Phenylethylmalonamide (PEMA). An important metabolite of primidone. Archives of Neurology (Chicago) 27: 34–41 (1972).CrossRefGoogle Scholar
  8. Blum, M.R.; Riegelman, S. and Becker, C.E.: Altered protein binding of diphenylhydantoin in uraemic plasma. New England Journal of Medicine 286: 109 (1972).PubMedGoogle Scholar
  9. Bochner, F.; Hooper, W.D.; Sutherland, J.M.; Eadie, M.J. and Tyrer, J.H.: Diphenylhydantoin concentrations in saliva. Archives of Neurology (Chicago) 31: 57–59 (1974).CrossRefGoogle Scholar
  10. Bochner, F.; Hooper, W.D.; Tyrer, J.H. and Eadie, M.J.: The effect of dosage increments on blood phenytoin concentrations. Journal of Neurology, Neurosurgery and Psychiatry 35: 873–876 (1972).CrossRefGoogle Scholar
  11. Booker, H.E.: Trimethadione and other oxazolidinediones. Relation of plasma levels to clinical control; in Woodbury, Penry and Schmidt (Eds) Antiepileptic Drugs, p.403–407 (Raven Press, New York 1972).Google Scholar
  12. Booker, H.E. and Celesia, G.G.: Serum concentrations of diazepam in subjects with epilepsy. Archives of Neurology (Chicago) 29: 191–194 (1973).CrossRefGoogle Scholar
  13. Booker, H.E. and Darcey, B.: Serum concentrations of free diphenylhydantoin and their relationship to clinical intoxication. Epilepsia (Amsterdam) 14: 177–184 (1973).CrossRefGoogle Scholar
  14. Buchanan, R.A.; Fernandez, L. and Kinkel, A.W.: Absorption and elimination of ethosuximide in children. Journal of Clinical Pharmacology 9: 393–398 (1969).Google Scholar
  15. Buchanan, R.A.; Kinkel, A.W.; Goulet, J.R. and Smith, T.C.: The metabolism of diphenylhydantoin (Dilantin) following once-daily administration. Neurology (Minneapolis) 22: 126–130 (1972).CrossRefGoogle Scholar
  16. 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).Google Scholar
  17. Buchthal, F. and Lennox-Buchthal, M.A.: Phenobarbital. Relation of serum concentration to control of seizures; in Woodbury, Penry and Schmidt (Eds) Antiepileptic Drugs, p.335–343 (Raven Press, New York 1972).Google Scholar
  18. Butler, T.C.: Metabolic demethylation of 3,5-dimethyl-5-ethyl 2,4-oxazolidinedione (paramethadione, Paradione®). Journal of Pharmacology and Experimental Therapeutics 113: 178–185 (1955).PubMedGoogle Scholar
  19. Butler, T.C.: The metabolic conversion of 5,5-diphenylhydantoin to 5-(p-hydroxyphenyl)-5-phenyl-hydantoin. Journal of Pharmacology and Experimental Therapeutics 119: 1–11 (1957).PubMedGoogle Scholar
  20. Chang, T.; Dill, W.A. and Glazko, A.J.: Ethosuximide. Absorption, distribution and excretion; in Woodbury, Penry and Schmidt (Eds) Antiepileptic Drugs, p.417–423 (Raven Press, New York 1972).Google Scholar
  21. 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).PubMedGoogle Scholar
  22. Craig, C.R. and Shideman, F.E.: Metabolism and anticonvulsant properties of mephobarbital and phenobarbital in rats. Journal of Pharmacology and Experimental Therapeutics 176: 35–41 (1971).PubMedGoogle Scholar
  23. De Silva, J.A.F. and Bekersky, I.: Determination of clonazepam and flunitrazepam in blood by electron-capture gas-liquid chromatography. Journal of Chromatography 99: 447–460 (1974).PubMedCrossRefGoogle Scholar
  24. De Silva, J.A.F.; Puglisi, C.V. and Munro, N.: Determination of clonazepam and flunitrazepam in blood and urine by electron-capture GLC. Journal of Pharmaceutical Sciences 63: 520–527 (1974).PubMedCrossRefGoogle Scholar
  25. Di Salle, E.; Pacifici, G.M. and Morselli, P.L.: Studies on plasma protein binding of carbamazepine. Pharmacology Research Communications 6: 193–202 (1974).CrossRefGoogle Scholar
  26. 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 (Minneapolis) 25: 255–258 (1975).CrossRefGoogle Scholar
  27. Eadie, M.J. and Tyrer, J.H.: Anticonvulsant Therapy. Pharmacological Basis and Practice (Churchill Livingstone, Edinburgh 1974).Google Scholar
  28. Ehrsson, H.: Gas chromatographic determination of barbiturates after extractive methylation in carbon disulfide. Analytical Chemistry 46: 922–924 (1974).PubMedCrossRefGoogle Scholar
  29. Ehrsson, H. and Tilly, A.: Electron capture gas chromatography of nitrazepam in human plasma as methyl derivative. Analytical Letters 6: 197–210 (1973).CrossRefGoogle Scholar
  30. Eichelbaum, M. and Bertilsson, L.: Determination of carbamazepine and its epoxide metabolite by high-speed liquid chromatography. Journal of Chromatography 103: 135–140(1975).PubMedCrossRefGoogle Scholar
  31. Eichelbaum, M.; Ekbom, K.; Bertilsson, L.; Ringberger, V.A. and Rane, A.: Plasma pharmacokinetics of carbamazepine and its epoxide metabolite in man after single and multiple doses. European Journal of Clinical Pharmacology 8: 337–341 (1975).PubMedCrossRefGoogle Scholar
  32. Evans, J.E.: Simultaneous measurement of diphenyl-hydantoin and phenobarbital in serum by high performance liquid chromatography. Analytical Chemistry 45: 2428–2429 (1973).CrossRefGoogle Scholar
  33. Firemark, H.; Barlow, C.F. and Roth, L.J.: The entry, accumulation and binding of diphenylhydantoin-2-C14 in brain. International Journal of Neuropharmacology 2:25–38 (1963).CrossRefGoogle Scholar
  34. Flynn, E.J. and Spector, S.: Determination of barbiturate derivatives by radioimmunoassay. Journal of Pharmacology and Experimental Therapeutics 181: 547–554 (1972).PubMedGoogle Scholar
  35. Gallagher, B.B. and Baumel, L.P.: Primidone. Absorption, distribution and excretion; in Woodbury, Penry and Schmidt (Eds) Antiepileptic Drugs, p.357–359 (Raven Press, New York 1972).Google Scholar
  36. Gallagher, B.B. and Baumel, L.P.: Primidone — biotransformation; in Woodbury, Penry and Schmidt (Eds) Antiepileptic Drugs, p.361–366 (Raven Press, New York 1972).Google Scholar
  37. Gallagher, B.B.; Smith, D.B. and Mattson, R.H.: The relationship of the anticonvulsant properties of primidone to phenobarbital. Epilepsia (Amsterdam) 11: 293–301 (1970).CrossRefGoogle Scholar
  38. Garrettson, L.K. and Dayton, P.G.: Disappearance of phenobarbital and diphenylhydantoin from serum of children. Clinical Pharmacology and Therapeutics 11: 674–679 (1970).PubMedGoogle Scholar
  39. Gauchel, G.; Gauchel, F.D. and Birkofer, L.: A micro-method for the determination of carbamazepine in blood by high speed liquid chromatography. Zeitschrift fur Klinische Chemie und Klinische Biochemie 11: 459–460 (1973).Google Scholar
  40. 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).PubMedGoogle Scholar
  41. Glazko, A.J. and Dill, W.A.: Other succinimides. Meth-suximide and phensuximide: in Woodbury, Penry and Schmidt (Eds) Antiepileptic Drugs, p.455–464 (Raven Press, New York 1972).Google Scholar
  42. Gouldie, J.H. and Burnett, D.: A gas-chromatographic method for the simultaneous determination of pheno-barbitone, primidone and phenytoin in serum using a nitrogen detector. Clinica Chimica Acta 43: 423–429 (1973).CrossRefGoogle Scholar
  43. Greeley, R.H.: New approach to derivatization and gas-chromatographic analysis of barbiturates. Clinical Chemistry 20: 192–194 (1974).PubMedGoogle Scholar
  44. Haerer, A.F. and Buchanan, R.A.: Effectiveness of single daily doses of diphenylhydantoin. Neurology (Minneapolis) 22: 1021–1025 (1972).CrossRefGoogle Scholar
  45. Hauptmann, A.: Luminal bei Epilepsie. Munchener medizinische Wochenschrift 59: 1907–1909 (1912).Google Scholar
  46. 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 (1974).PubMedGoogle Scholar
  47. Hooper, W.D.; Dubetz, 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).PubMedGoogle Scholar
  48. Hooper, W.D.; Dubetz, D.K.; Eadie, M.J. and Tyrer, J.H.: Preliminary observations on the clinical pharmacology of carbamazepine (’Tegretol’). Proceedings of the Australian Association of Neurologists 11: 189–198 (1974).PubMedGoogle Scholar
  49. Horning, M.G.; Lertratanangkoon, K.; Nowlin, J.; Stillwell, W.G.; Stilwell, R.N.; Zion, T.E. and Kellaway, P.: Anticonvulsant drug monitoring by GC-MS-COM techniques. Journal of the Chromatographic Sciences 12: 630–635 (1974).Google Scholar
  50. Horning, M.G.; Stratton, C.; Nowlin, J.; Harvey, D.J. and Hill, R.M.: Metabolism of 2-ethyl-2-methylsuccinimide (Ethosuximide) in the rat and human. Drug Metabolism and Distribution 1: 569–576 (1973).Google Scholar
  51. Johannessen, S.I. and Strandjord, R.E.: Concentration of carbamazepine (Tegretol® in serum and cerebrospinal fluid in patients with epilepsy. Epilepsia (Amsterdam) 14: 373–379 (1973).CrossRefGoogle Scholar
  52. 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).PubMedCrossRefGoogle Scholar
  53. 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).PubMedCrossRefGoogle Scholar
  54. Knop, H.J.; Van der Kleijn, E. and Edmunds, L.C.: The determination of clonazepam in plasma by gas-liquid chromatography. Pharmaceutisch Weekblad 110: 297–309 (1975).Google Scholar
  55. Kutt, H.: Interactions of antiepileptic drugs. Epilepsia (Amsterdam) 16: 393–402 (1975).CrossRefGoogle Scholar
  56. Lander, C.M.; Edwards, V.E.; Eadie, M.J. and Tyrer, J.H.: Plasma anticonvulsant concentrations during pregnancy. Submitted for publication.Google Scholar
  57. Lund, L.: Anticonvulsant effect of diphenylhydantoin relative to plasma levels. A prospective three-year study in ambulant patients with generalized epileptic seizures. Archives of Neurology (Chicago) 31: 289–294 (1974).Google Scholar
  58. 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).Google Scholar
  59. Lund, M.: Failure to observe dosage instructions in patients with epilepsy. The short-term effect of a daily dispenser. Acta Neurologica Scandinavica 49: 295–306 (1973).Google Scholar
  60. Lund, M.; Jorgensen, R.S. and Kuhl, V.: Serum diphenylhydantoin (phenytoin) in ambulant patients with epilepsy. Epilepsia (Amsterdam) 5: 51–58 (1964).CrossRefGoogle Scholar
  61. 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 (1973).Google Scholar
  62. Mark, L.C.: Metabolism of barbiturates in man. Clinical Pharmacology and Therapeutics 4: 504–530 (1963).Google Scholar
  63. 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).PubMedCrossRefGoogle Scholar
  64. Meijer, J.W.A.; Meinardi, H.; Gardner-Thorpe, C. and Van der Kleijn, E.: Methods of Analysis of Anti-epileptic Drugs (Excerpta Medica, Amsterdam, 1973).Google Scholar
  65. Meinardi, H.: Other antiepileptic drugs. Carbamazepine; in Woodbury, Penry and Schmidt (Eds) Antiepileptic Drugs, p.487–496 (Raven Press, New York 1972).Google Scholar
  66. Meinardi, H.: Discussion; in Meijer, Meinardi, Gardner Thorpe and Van der Kleijn (Eds) Methods of Analysis of Anti-epileptic Drugs, p. 211 (Excerpta Medica, Amsterdam 1973).Google Scholar
  67. Meinardi, H.; Van der Kleijn, E.; Meijer, J.W.A. and Van Rees, H.: Absorption and distribution of antiepileptic drugs. Epilepsia (Amsterdam) 16: 353–365 (1975).CrossRefGoogle Scholar
  68. Montgomery, M.R.; Holtzman, J.L.; Leute, R.K.; Dewees, J.S. and Bolz, G.: Determination of diphenylhydantoin in human serum by spin immunoassay. Clinical Chemistry 21: 221–226 (1975).PubMedGoogle Scholar
  69. Morrison, L.D. and O’Donnell, C.M.: Determination of diphenylhydantoin by phosphorescence spectrometry. Analytical Chemistry 46: 1119–1120 (1974).PubMedCrossRefGoogle Scholar
  70. Morselli, P.L.: Discussion; in Meijer, Meinardi, Gardner Thorpe and Van der Kleijn (Eds) Methods of Analysis of Anti-epileptic Drugs, p. 175 (Excerpta Medica, Amsterdam 1973).Google Scholar
  71. Morselli, P.L.; Principi, N.; Tognoni, G.; Reali, E.; Belvedere, G.; Standen, S.M. and Sereni, F.: Diazepam elimination in premature and full term infants, and children. Journal of Perinatal Medicine 1: 133–141 (1973).PubMedCrossRefGoogle Scholar
  72. Müller, W. and Wollert, U.: Characterization of the binding of benzodiazepines to human serum albumin. Naunyn-Schmiedeberg’s Archives of Pharmacology 280: 229–237 (1973).PubMedCrossRefGoogle Scholar
  73. Odar-Cederlöf, I.; Lunde, P. and Sjöqvist, F.: Abnormal pharmacokinetics of phenytoin in a patient with uraemia. Lancet 2: 831–832 (1970).PubMedCrossRefGoogle Scholar
  74. Palmer, L.; Bertilsson, L.; Collste, P. and Rawlins, M.: Quantitative determination of carbamazepine in plasma by mass fragmentography. Clinical Pharmacology and Therapeutics 14: 827–832 (1973).PubMedGoogle Scholar
  75. Peskar, B. and Spector, S.: Quantitative determination of diazepam in blood by radioimmunoassay. Journal of Pharmacology and Experimental Therapeutics 186: 167–172 (1973).PubMedGoogle Scholar
  76. Randall, L.O.; Scheckel, C.L. and Banziger, R.: Pharmacology of the metabolites of chlordiazepoxide and diazepam. Current Therapeutic Research 1: 590–606 (1965).Google Scholar
  77. Reidenberg, M.M.; Odar-Cederlöf, I.; von Bahr, G.; Borgå, A. and Sjöqvist, F.: Protein binding of diphenylhydantoin and desmethylimipramine in plasma from patients with poor renal function. New England Journal of Medicine 285: 264–267 (1971).PubMedCrossRefGoogle Scholar
  78. Richens, A.: Drug estimation in the treatment of epilepsy. Proceedings of the Royal Society of Medicine 67: 1227–1229 (1974).PubMedGoogle Scholar
  79. Rieder, J. and Wendt, G.: Pharmacokinetics and metabolism of the hypnotic nitrazepam. Symposium on Benzodiazepines, Milan (1971).Google Scholar
  80. Rowan, A.J.; Pippenger, C.E.; McGregor, P.A. and French, J.H.: Seizure activity and anticonvulsant drug concentration. Archives of Neurology (Chicago) 32: 281–288 (1975).CrossRefGoogle Scholar
  81. 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).PubMedCrossRefGoogle Scholar
  82. Sherwin, A.L. and Robb, J.P.: Ethosuximide: Relation of plasma level to clinical control; in Woodbury, Penry and Schmidt (Eds) Antiepileptic Drugs, p.443–448 (Raven Press, New York 1972).Google Scholar
  83. Shoeman, D.W. and Azarnoff, D.L.: The alteration of plasma proteins in uremia as reflected in their ability to bind digitoxin and diphenylhydantoin. Pharmacology 7: 169–177(1972).PubMedCrossRefGoogle Scholar
  84. Spector, S. and Flynn, E.J.: Barbiturates: radioimmunoassay. Science 174: 1036–1038 (1971).PubMedCrossRefGoogle Scholar
  85. Strandjord, R.E. and Johannessen, S.I.: One daily dose of diphenylhydantoin (DPH) to patients with epilepsy. Acta Neurologica Scandinavica 48 (Suppl 51): 499–500 (1972).Google Scholar
  86. Strandjord, R.E. and Johannessen, S.I.: One daily dose of diphenylhydantoin for patients with epilepsy. Epilepsia (Amsterdam) 15: 317–327 (1974).CrossRefGoogle Scholar
  87. Terrence, C.F. Jr.; Wisotzkey, H.M. and Perper, J.A.: Unexpected, unexplained death in epileptic patients. Neurology (Minneapolis) 25: 594–598 (1975).CrossRefGoogle Scholar
  88. Tigelaar, R.E.; Rapport, R.L. II; Inman, J.K. and Kupferberg, H.J.: A radioimmunoassay for diphenylhydantoin. dinica Chimica Acta 43: 231–241 (1973).CrossRefGoogle Scholar
  89. Triedman, H.M.; Fishman, R.A. and Yahr, M.D.: Determination of plasma and cerebrospinal fluid levels of Dilantin in the human. Transactions of the American Neurological Association 85: 166–170 (1960).PubMedGoogle Scholar
  90. Troupin, A.S. and Friel, P.: Anticonvulsant level in saliva, serum, and cerebrospinal fluid. Epilepsia (Amsterdam) 16: 223–227 (1975).CrossRefGoogle Scholar
  91. Vajda, F.J.E.; Merory, J. and Bladin, P.F.: Fluctuations of plasma phenytoin levels on single dose and twice daily dose regimes. Proceedings of the Australian Association of Neurologists 12: 61–64 (1975).PubMedGoogle Scholar
  92. Van der Kleijn, E.; Guellen, P.J.M.; Van Wijk, C.G.W.M.; Baars, I. and Vree, T.B.: Clinical pharmacokinetics of benzodiazepines, barbiturates and short chain fatty acids; in Levy (Ed) Clinical Pharmacokinetics, p.79–101 (American Pharmaceutical Association, Washington 1974).Google Scholar
  93. Van der Kleijn, 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).Google Scholar
  94. Venturella, V.S.; Gualario, V.M. and Lang, R.E.: Dimethyl-formamide diethylacetyl as a derivatizing agent for GLC of barbiturates and related compounds. Journal of Pharmaceutical Sciences 62: 662–668 (1973).PubMedCrossRefGoogle Scholar
  95. Wallace, J.E.; Farquhar, J.K.; Hamilton, H.E. and Everhart, B.A.: Comments on the determination of diphenylhydantoin. Clinical Chemistry 20: 515–516 (1974).PubMedGoogle Scholar
  96. 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).PubMedCrossRefGoogle Scholar
  97. Wilson, J.T. and Wilkinson, G.R.: Delivery of anticonvulsant drug therapy in epileptic patients assessed by plasma level analyses. Neurology (Minneapolis) 24: 614–623 (1974).CrossRefGoogle Scholar
  98. Wolf, S.M.; Carr, A.C.; Hanson, R.A.; Dale, E.P.; Davis, D.C.; Goldenberg, E.D.; Lulejian, G.A.; Sharpe, K.S.; Trietman, P. and Weinstein, A.W.: Parental compliance in the continuous administration of phenobarbital for the prevention of febrile seizures. Journal of Pediatrics 83: 1085–1086 (1973).PubMedCrossRefGoogle Scholar
  99. Woodbury, D.M.; Penry, J.K. and Schmidt, R.: Antiepileptic Drugs (Raven Press, New York 1972).Google Scholar

Copyright information

© ADIS Press 1976

Authors and Affiliations

  • M. J. Eadie
    • 1
  1. 1.Department of MedicineUniversity of QueenslandBrisbaneAustralia

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