Advertisement

Clinical Pharmacokinetics

, Volume 6, Issue 1, pp 1–24 | Cite as

Clinical Implications of Enzyme Induction and Enzyme Inhibition

  • B. K. Park
  • A. M. Breckenridge
Article

Summary

The pharmacological effect of a drug is partly dependent upon its concentration at its site of action, which in turn is partly dependent upon its rate of elimination. The rate of elimination of many lipophilic drugs is governed by the activity of the hepatic microsomal mixed-function oxidases. Consequently any alteration in the activity of these enzymes may result in a modification of drug action. A wide range of chemically unrelated substances may stimulate the activity of the mixedfunction oxidases by enzyme induction. The drugs most frequently encountered as enzymeinducing agents in man are barbiturates, rifampicin and Phenytoin. Enhancement of drug metabolism by ethanol, tobacco smoking and diet may also involve enzyme induction. Enzyme induction is normally associated with a reduction in drug efficacy but may also alter the toxicity of certain substances.

Enzyme induction has been assessed in man by measuring changes in the pharmacokinetics of a marker drug, or changes in the disposition of endogenous compounds such as γ-glutamyltranspeptidase, D-glucaric acid and 6β-hydroxycortisol.

The therapeutic problems associated with enzyme inhibition have received much less attention than those associated with enzyme induction. The effect on the rate of elimination of a particular drug will depend upon the fraction of the dose that is normally metabolised by the inhibited enzyme and on the affinity of the enzyme for the drug and the inhibitor. An alteration in the dosage schedule is usually only necessary for drugs with a small therapeutic ratio.

Keywords

Clinical Pharmacology Rifampicin Tolbutamide Antipyrine Enzyme Induction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aarts, E.M.: Evidence for the function of D-glucaric acid as an indicator for drug induced enhanced metabolism through the glucuronic pathway in man. Biochemical Pharmacology 11: 359–363 (1965).CrossRefGoogle Scholar
  2. Aarts, E.M.: D-glucaric acid excretion as a test for hepatic enzyme induction. Lancet 1: 859 (1971).PubMedCrossRefGoogle Scholar
  3. Acocella, G.; Pangani, V.; Narchetti, M.; Baroni, G.C. and Nicolis, F.B.: Kinetic studies on rifampicin. I. Serum concentration analysis in subjects treated with different oral doses over a period of two weeks. Chemotherapy 16: 356–370 (1971).PubMedCrossRefGoogle Scholar
  4. Acocella, G.; Mattiusi, R. and Tenconi, L.T.: Serum concentrations and biliary excretion of bnirubin during short term treatment with rifampicin. Tijdschrift voor Gastroenterologie 16: 186–190 (1973).Google Scholar
  5. Acocella G.; Nattiussi, R. and Segre, G.: Multicompartmental analysis of serum, urine and bile concentrations of rifampicin and desacetyl-rifampicin in subjects treated for one week. Pharmacological Research Communications 10: 271–288 (1978).PubMedCrossRefGoogle Scholar
  6. Anders, M.W. and Mannering, G.J.: Inhibition of drug metabolism. IV. Induction of drug metabolism by 2,2-diethylaminoethyl-2,2-diphenylvalerate HCl (SKF 525-A) and 2,4-dichloro-6-phenylphenoxyethylamine HBr (Lilly 18947) and the effect of induction on the inhibitory properties of SKF 525-A type compounds. Molecular Pharmacology 2: 341–346 (1966).PubMedGoogle Scholar
  7. Antlintz, M.A.; Tolentino, M. and Kosai, MF.: Effect of Butabarbital on orally administered anticoagulants. Current Therapeutic Research 10: 70–73 (1968).Google Scholar
  8. Arcos, J.C.; Conney, A.H.; Buu-Hoi, N.P.: Induction of microsomal enzyme synthesis by polycyclic aromatic hydrocarbons of different molecular sizes. Journal of Biological Sciences 236: 1291–1296 (1961).Google Scholar
  9. Arnold, K. and Gerber, N.: The rate of decline of diphenylhydantoin in human plasma. Clinical Pharmacology and Therapeutics 11: 121–134 (1970).PubMedGoogle Scholar
  10. Back, D.J.; Breckenridge, A.M.; Gay, F.E.; Orme, M.L.E.; Rowe, P.H. and Smith, E.: in Haspels and Kay (Eds) International Symposium on Hormonal Contraception, p. 169 (Excerpta Medica, Amsterdam 1978).Google Scholar
  11. Back, D.J.; Breckenridge, A.M.; Crawford, F.E., MacIver, M.; Orme, M.L’E.; Park, B.K.; Rowe, P.H. and Smith, E.: The effect of rifampicin on norethisterone pharmacokinetics. European Journal of Clinical Pharmacology 15: 193–197 (1979).PubMedCrossRefGoogle Scholar
  12. Ballinger, B.; Browning, M.; O’Malley, K. and Stevenson, I.H.: Drug metabolising capacity in states of drug dependence and withdrawal. British Journal of Pharmacology 45: 638–643 (1972).PubMedCrossRefGoogle Scholar
  13. Beran, G.: Der Einfluss der Rifampizintherapie auf die orale Antikoagulation mit Acenocoumarol. Praxis und Klinik der Pneumologie 26: 350–353 (1972).Google Scholar
  14. Berman, M.L. and Green, O.C.: Acute stimulation of Cortisol metabolism by pentobarbital in man. Anesthesiology 34: 365–369 (1971).PubMedCrossRefGoogle Scholar
  15. Birmingham, AT.; Coleman, A.J.; Orme, M.L.’E.; Park, B.K.; Pearson, N.; Short, A.M. and Southgate, P.J.: Antibacterial activity in serum and urine following oral administration in man of DL 473 (a cyclopentyl derivative of rifampicin). British Journal of Clinical Pharmacology 6: 455P (1978).CrossRefGoogle Scholar
  16. Black, M. and Sherlock, S.: Treatment of Gilbert’s syndrome with phenobarbitone. Lancet 1: 1359–1362 (1970).PubMedCrossRefGoogle Scholar
  17. Black, M.; Fevery, J.; Parker, D.; Jacobson, J.; Billing, B.H. and Carson, E.R.: Effect of phenobarbitone on plasma [14C] bilirubin hyperbilirubinaemia. Clinical Science and Molecular Medicine 46: 1–17 (1974).PubMedGoogle Scholar
  18. Bledsoe, T.; Island, D.P.; Ney, R.L. and Liddle, G.W.: An effect of o,p’-DDD on the extra-renal metabolism of Cortisol in man. Journal of Clinical Endocrinology and Metabolism 24: 1303–1311 (1964).PubMedCrossRefGoogle Scholar
  19. Bogaert, M.G.; Rosseel, MT. and Belpaine, F.M.: Metabolism of nitroglycerine in man: influence of phenobarbital. Archives Internationales de Pharmacodynamie et de Therapeutie 192: 198–199 (1971).Google Scholar
  20. Bolt, H.M.; Kappus, H. and Bolt, U.: Effect of rifampicin treatment on the metabolism of oestradiol and 17α-ethinyloestradiol by human liver microsomes. European Journal of Clinical Pharmacology 8: 301–307 (1975).PubMedCrossRefGoogle Scholar
  21. Bolt, H.M.; Bolt, M. and Kappus, H.: Interaction of Rifampicin treatment with pharmacokinetics and metabolism of ethinyloestradiol in man. Acta Endocrinologica 85: 189–197 (1977).PubMedGoogle Scholar
  22. Boyd, M.R.: Evidence for the Clara cell as a site of cytochrome P450-dependent mixed-function oxidase activity in the lung. Nature 269: 713–715 (1977).PubMedCrossRefGoogle Scholar
  23. Branch, R.A.; Shand, D.G.; Wilkinson, G.R. and Nies, A.: Increased clearance of antipyrine and Propranolol after phenobarbital treatment in monkey. Journal of Clinical Investigation 53: 1101–1107 (1974).PubMedCrossRefGoogle Scholar
  24. Breckenridge, A.M. and Orme, M.L.E.: Clinical implications of enzyme induction. Annals of the New York Academy of Sciences 179: 421–431 (1971).PubMedCrossRefGoogle Scholar
  25. Breckenridge, A.M.; Orme, M.L.E.; Thorgeirsson, S.S.; Davies, D.S. and Brooks, R.K.: Drug interactions with warfarin: Studies with dichloralphenazone, chloral hydrate and Phenazone (antipyrine). Clinical Science 40: 351–364 (1971).PubMedGoogle Scholar
  26. Breckenridge, A.; Orme, M.L.E.; Davies, L.; Thorgeirsson, S.S. and Davies, D.S.: Dose-dependent enzyme induction. Clinical Pharmacology and Therapeutics 14: 514–520 (1973).PubMedGoogle Scholar
  27. Breckenridge, A.; Bending, M.R. and Brunner, G.: in Ulruch (Ed) Microsomes and Drug Oxidations, p.385 (Pergamon, Oxford 1977).Google Scholar
  28. Breimer, D.D.; Zilly, W. and Richter, M.D.: Influence of rifampicin on drug metabolism: Differences between hexobarbital and antipyrine. Clinical Pharmacology and Therapeutics 21: 470–481 (1977).PubMedGoogle Scholar
  29. Brodie, M.J.; Boobis, A.R.; Dollery, C.T.; Hillyard, C.J.; Brown, D.J.; MacIntyre, I. and Park, B.K.: Rifampicin and Vitamin D metabolism in man. Clinical Pharmacology and Therapeutics 27: 810–814 (1980).PubMedCrossRefGoogle Scholar
  30. Brooks, P.M.; Bell, MA. and Burns, H.: Salivary antipyrine half-life: A useful measure of hepatic drug metabolism. British Journal of Clinical Pharmacology 3: 945–946 (1976).PubMedCrossRefGoogle Scholar
  31. Buchanan, R.A. and Sholiton, L.J.: in Woodbury, Perry, and Schmidt (Eds) Antiepileptic Drugs, p. 181 (Raven Press, New York 1972).Google Scholar
  32. Burstein, S. and Klaiber, E.L.: Phenobarbital-induced increase in 6-beta-hydroxycortisol excretion: clue to its significance in urine. Journal of Clinical Endocrinology and Metabolism 25: 293–296 (1965).PubMedCrossRefGoogle Scholar
  33. Busfield, D.; Child, K.J.; Atkinson, R.M. and Tomich, E.G.: An effect of phenobarbitone on blood-levels of griseofulvin in man. Lancet 2: 1042–1043 (1963).PubMedCrossRefGoogle Scholar
  34. Calne, D.B.: The drug treatment of epilepsy. British Journal of Hospital Medicine 9: 171–175 (1973).Google Scholar
  35. Chang, R.L.; Wood, A.W.; Dixon, W.R.; Conney, AH.; Anderson, K.E.; Eiseman, J. and Alvares, A.P.: Antipyrine: Radioimmunoassay in plasma and saliva following administration of a high dose and a low dose. Clinical Pharmacology and Therapeutics 20: 219–226 (1976).PubMedGoogle Scholar
  36. Chen, W.; Vrindten, P.A.; Dayton, P.G. and Burns, J.: Accelerated aminopyrine metabolism in human subjects pretreated with Phenylbutazone. Life Sciences 2: 35–42 (1962).CrossRefGoogle Scholar
  37. Choi, Y.; Thrasher, K.; Werk, 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).PubMedGoogle Scholar
  38. Christensen, L.K. and Kristensen, M.: Drug induced changes of the blood glucose lowering effect of oral hypoglycemic agents. Acta Diabetologica Latina (Suppl) 1: 116–136 (1969).Google Scholar
  39. Christensen, L.K.; Hansen, J.M. and Kristensen, M.: Sulphaphenazole-induced hypoglycaemic attacks in Tolbutamidetreated diabetics. Lancet 2: 1298 (1963).PubMedCrossRefGoogle Scholar
  40. Conney, A.H.: Pharmacological implications of microsomal enzyme induction. Pharmacological Reviews 19: 317–356 (1967).PubMedGoogle Scholar
  41. Corn, M.: Effect of phenobarbital and glutethimide on biological half-life of warfarin. Thrombosis et Diathesis Haemorrhagica 16: 606–612 (1966).PubMedGoogle Scholar
  42. Crigler, J.F. and Gold, N.I.: Sodium phenobarbital-induced decrease in serum bilirubin in an infant with congenital jaundice and kernicterus. Journal of Clinical Investigation 45: 998–999 (1966).Google Scholar
  43. 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 (Dicoumarol) and diphenylhydantoin (Dilantin). Clinical Pharmacology and Therapeutics 6: 420–429 (1965).PubMedGoogle Scholar
  44. Danhof, M. and Breimer, D.D.: Studies on the different metabolic pathways of antipyrine in man. I. Oral administration of 250, 500 and 1000mg to healthy volunteers. British Journal of Clinical Pharmacology 8: 529–537 (1979).PubMedCrossRefGoogle Scholar
  45. Dayton, P.G.; Tarcan, Y.; Chenkin, T. and Weiner, W.: The influence of barbiturates on coumarin plasma levels and prothrombin response. Journal of Clinical Investigation 40: 1797–1802 (1961).PubMedCrossRefGoogle Scholar
  46. Dent, C.E.; Richens, A.; Rowe, D.J.R. and Stamp, T.C.B.: Osteomalacia with long-term anticonvulsant therapy in epilepsy. British Medical Journal 4: 69 (1970).PubMedCrossRefGoogle Scholar
  47. De Rautlin de la Roy, Y.; Beuchant, G.; Breuil, K. and Patt, F.: Diminution du taux serique de rifampicine par le phenobarbital. Nouvelle Presse Medicale 79: 350 (1971).Google Scholar
  48. Douglas, J.F.; Ludwig, B.J. and Smith, N.: Studies on the metabolism of meprobamate. Proceedings of the Society of Experimental Biology and Medicine 112: 436–438 (1963).Google Scholar
  49. Edwards, O.M.; Courtenay-Evans, R.; Galley, J.; Hunter, J. and Tait, A.J.: Changes in cortisol metabolism following rifampicin therapy. Lancet 2: 549–551 (1974).CrossRefGoogle Scholar
  50. Estabrook, R.W. and Lindenlaub, E. (Eds): The Induction of Drug Metabolism (Shattauer-Verlag, Stuttgart 1979).Google Scholar
  51. Fahim, M.S.; Hall, D.G. and Fahim, Z.: Urinary D-glucaric acid. An index of hepatic microsomal enzyme activity in human females. American Journal of Obstetrics and Gynecology 105: 124–126 (1969).PubMedGoogle Scholar
  52. Forrest, F.M.; Forrest, I.M. and Serra, M.T.: Modification of chlorpromazine metabolism by some other drugs frequently administered to psychiatric patients. Biological Psychiatry 2: 53–58 (1970).PubMedGoogle Scholar
  53. Frantz, A.G.; Katz, F.H. and Jailer, J.N.: 6β-Hydroxycortisol and other polar corticosteroids: Measurement and significance in human urine. Journal of Clinical Endocrinology 21: 1290–1303 (1961).CrossRefGoogle Scholar
  54. Gelber, R.H.; Gooi, H.C. and Rees, R.J.W.: The effect of rifampicin on dapsone metabolism. Proceedings of the Western Pharmacological Society 18: 330–334 (1975).Google Scholar
  55. Gelehrter, T.D.: Enzyme induction. New England Journal of Medicine 294: 522–526, 589-595, 646-651 (1976).PubMedCrossRefGoogle Scholar
  56. Goldstein, A.; Aronow, L. and Kaiman, S.M.: in Principles of Drug Action, p.329 (John Wiley & Son, London 1974).Google Scholar
  57. Hahn, T.J.; Bendin, B.A.; Scharp, C.R. and Haddad, J.G.: Effect of chronic anticonvulsant therapy on serum 25-hydroxy-cholecalciferol levels in adults. New England Journal of Medicine 287: 900–903 (1972).PubMedCrossRefGoogle Scholar
  58. Hald, J. and Jacobsen, E.: The formation of acetaldehyde in the organism after ingestion of antabuse (tetraethylthiuramdisulphide) and alcohol. Acta Pharmacologica et Toxicologia 4: 305–310 (1948).CrossRefGoogle Scholar
  59. Hammer, W. and Sjoqvist, F.: Plasma levels of monomethylated tricyclic antidepressants during treatment with imipraminelike compounds. Life Sciences 6: 1895–1903 (1967).PubMedCrossRefGoogle Scholar
  60. Hansen, J.M. and Christensen, L.K.: Drug interactions with oral sulpharylurea hypoglycaemic drugs. Drugs 13: 24–34 (1977).PubMedCrossRefGoogle Scholar
  61. Hansen, J.M.; Siersboek-Nielsen, K.; Kristensen, M.; Skousted, L. and Christensen, L.K.: Effect of diphenylhydantoin on the metabolism of dicoumarol in man. Acta Medica Scandinavia 189: 15–19 (1971a).CrossRefGoogle Scholar
  62. 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).PubMedGoogle Scholar
  63. Hawkins, C.F. and Meynell, M.J.: Megaloblastic anaemia due to Phenytoin sodium. Lancet 2: 737–738 (1954).CrossRefGoogle Scholar
  64. Held, H.; Schoene, B.; Laar, H.J. and Fleischmann, R.: Die Aktivität der Benzpyrenhydrozylase im Leberpunktat des Menschen in vitro und ihre Beziehung zur Eliminations-geschwindigkeir von glycodiazin in vivo. Verhandlungen der Deutschen Gesellshaft für Inhere Medizin 80: 501–503 (1974).Google Scholar
  65. Helleberg, L.; Rubin, A.; Wolen, R.L.; Rodda, B.E.; Ridolfo, A.S. and Gruber, C.M.; A pharmacokinetic interaction in man between phenobarbitone and fenoprofen, a new anti-inflammatory agent. British Journal of Clinical Pharmacology 1: 371–377 (1974).PubMedCrossRefGoogle Scholar
  66. Hempel, E.; Bohm, W.; Carol, W. and Klinger, G.: Medikamentose Enzyminduktion und hormonale Kontrazeption. Zentrablatt fur Gynakologie 95: 1451–1457 (1973).Google Scholar
  67. Hildebrandt, A.G.; Roots, I.; Speck, M.; Saalfrank, K. and Kewitz, H.: Evaluation of in vivo parameters of drug metabolising enzyme activity in man after administration of Clemastine, Phenobarbital or Placebo. European Journal of Clinical Pharmacology 8: 327–336 (1975).PubMedCrossRefGoogle Scholar
  68. Hoffbrand, A.V. and Necheles, T.F.: Mechanism of folate deficiency in patients receiving Phenytoin. Lancet 2: 528–530 (1968).PubMedCrossRefGoogle Scholar
  69. Houston, J.B.: Effect of vitamin C supplement on antipyrine disposition in man. British Journal of Clinical Pharmacology 4: 236–239 (1977).PubMedCrossRefGoogle Scholar
  70. Huffman, D.H.; Shoeman, D.W.; Pentikainen, D. and Azarnoff, D.L.: The effect of Spironolactone on antipyrine metabolism in man. Pharmacology 10: 338–344 (1973).PubMedCrossRefGoogle Scholar
  71. Hunter, J.; Maxwell, J.D.; Carella, M.; Stewart, D.A. and Williams, R.: Urinary D-glucaric-acid excretion as a test for hepatic enzyme induction in man. Lancet 1: 572–575 (1971a).PubMedCrossRefGoogle Scholar
  72. Hunter, J.; Maxwell, J.D.; Stewart, D.A.; Williams, R.; Robinson, J. and Richardson, A.: Environmental exposure to organochlorine pesticides and hepatic enzyme induction in man. Gut 12: 761 (1971b).Google Scholar
  73. Hunter, J.; Maxwell, J.D.; Stewart, D.A. and Williams, R.: Urinary D-glucaric acid excretion and total liver content of Cytochrome P-450 in guinea-pigs: Relationship during enzyme induction and following inhibition of protein synthesis. Biochemical Pharmacology 22: 743–747 (1973).PubMedCrossRefGoogle Scholar
  74. Hunter, J.; Burnham, W.R.; Chasseaud, L.F. and Down, W.: Changes in D-glucaric acid excretion in relationship to alterations in the rate of antipyrine metabolism in man. Biochemical Pharmacology 23: 2480–2483 (1974).PubMedCrossRefGoogle Scholar
  75. Hutson, D.H.: in Hathway (Ed) Foreign Compound Metabolism in Mammals — Vol. III, p.493 (Chemical Society, 1975).Google Scholar
  76. Hussar, D.A.: Oral anticoagulants — their interactions. Journal of American Pharmacy Association 10: 78–82 (1970).Google Scholar
  77. Ioannides, D. and Parke, D.V.: Mechanism of induction of hepatic microsomal drug metabolising enzymes by a series of barbiturates. Journal of Pharmacy and Pharmacology 27: 739–746 (1975).PubMedCrossRefGoogle Scholar
  78. Jackson, L.; Homeida, M. and Roberts, C.J.C.: The features of hepatic enzyme induction with glutethimide. British Journal of Clinical Pharmacology 6: 525–528 (1978).PubMedCrossRefGoogle Scholar
  79. Jager, K.W.: in Aldrin, Dieldrin, Endrin and Telodrin: on epidemiological and toxicological study of long term occupational exposure (Elsevier, Amsterdam 1970).Google Scholar
  80. Jezequel, A.M.; Orlandi, F. and Tenconi, L.T.: Changes of the smooth endoplasmic reticulum induced by rifampicin in human and guinea-pig hepatocytes. Gut 12: 984–987 (1971).PubMedCrossRefGoogle Scholar
  81. Johannson, S.A.: Apparent resistance to oral anticoagulant therapy and influence of hypnotics on some coagulation factors. Acta Medica Scandinavica 184: 297–300 (1968).CrossRefGoogle Scholar
  82. Johnsen, S.G.; Kampmann, J.P.; Bennet, E.P. and Jorgensen, F.S.: Enzyme induction by oral testosterone. Clinical Pharmacology and Therapeutics 20: 233–237 (1976).Google Scholar
  83. Jubiz, W.; Meikle, A.W.; Levinson, R.A; Mizutani, S.; West, C.D. and Tyler, F.H.: Effect of diphenylhydantoin on the metabolism of dexamethasone. New England Journal of Medicine 283: 11–24 (1970).PubMedCrossRefGoogle Scholar
  84. Jusko, W.J.: Role of tobacco smoking in pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics 6: 7–39 (1978).PubMedCrossRefGoogle Scholar
  85. Kahn, G.C.; Boobis, A.R.; Blair, I.; Brodie, M.J. and Davies, D.S.: Antipyrine as an in vitro probe of mixed function oxidase activity. British J. Clin. Pharmacol. 9: 284P (1980).CrossRefGoogle Scholar
  86. Kappas, A.; Anderson, K.E.; Conney, A.H. and Alvares, A.P.: Influence of dietary protein and carbohydrate on antipyrine and theophylline metabolism in man. Clinical Pharmacology and Therapeutics 20: 643–653 (1976).PubMedGoogle Scholar
  87. Kappas, A.; Alvares, A.P.; Anderson, K.E.; Pantuck, E.J.; Chang, R. and Conney, A.H.: Effect of charcoal-broiled beef on antipyrine and theophylline metabolism. Clinical Pharmacology and Therapeutics 23: 445–450 (1978).PubMedGoogle Scholar
  88. Kanto, J.; Iisalo, E.; Lehtinen, V. and Salminen, J.: The concentrations of diazepam and its metabolites in the plasma after acute and chronic administration. Psychopharmacologia 36: 123–131 (1974).PubMedCrossRefGoogle Scholar
  89. Kater, R.M.H.; Tobon, F. and Iber, F.L.: Increased rate of tolbutamide metabolism in alcoholic patients. Journal of American Medical Association 207: 363–365 (1969).CrossRefGoogle Scholar
  90. Kawada, M.; Yamada, K.; Kagawa, Y. and Mano, Y.: Effect of some drugs on lactonase activity of rat liver. Journal of Biochemistry (Tokyo) 50: 74–76 (1961).Google Scholar
  91. Kolmodin, B.; Azarnoff, D.L. and Sjoqvist, F.: Effect of environmental factors on drug metabolism: Decreased plasma half-life of antipyrine in workers exposed to hydrocarbon insecticides. Clinical Pharmacology and Therapeutics 10: 638–642 (1969).PubMedGoogle Scholar
  92. Kreek, M.J. and Sleisenger, M.H.: Reduction of serum-unconjugated-bilirubin with phenobarbitone in adult congenital nonhaemolytic unconjugated hyperbilirubinaemia. Lancet 2: 73–77 (1968).CrossRefGoogle Scholar
  93. Kuntzman, R.; Jacobson, M. and Conney, A.H.: Effect of Phenylbutazone on cortisol metabolism in man. Pharmacologist 8: 195 (1966).Google Scholar
  94. Kutt, H.: Biochemical and genetic factors regulating dilantin metabolism in man. Annals of the New York Academy of Sciences 179: 705–722 (1971).PubMedCrossRefGoogle Scholar
  95. Kutt, H.; Haynes, J.; Verebely, K. and McDowell, F.: The effect of phenobarbital on plasma diphenylhydantoin level and metabolism in man and in rat liver microsomes. Neurology (Minneapolis) 19: 611–616 (1969).CrossRefGoogle Scholar
  96. Kutt, H.; Brennan, R.; Dehijia, H. and Verebely, K.: Diphenylhydantoin intoxication. A complication of isoniazid therapy. American Review of Respiratory Disease 101: 377–384 (1970).PubMedGoogle Scholar
  97. Labadarios, D.; Dickerson, J.W.T.; Parke, D.V.; Lucas, E.G. and Obuwa, G.H.: The effects of chronic drug administration on hepatic enzyme induction and alcohol in man. British Journal of Clinical Pharmacology 5: 167–174 (1978).PubMedCrossRefGoogle Scholar
  98. Lai, A.A.; Levy, R.H. and Cutler, R.E.: Time-course of interaction between carbamazepine and clonazepam in normal man. Clinical Pharmacology and Therapeutics 24: 316–323 (1978).PubMedGoogle Scholar
  99. Larsen, P.R.; Atkinson, A.J.; Wellman, H.N. and Goldsmith, R.E.: The effect of diphenylhydantoin on thyroxine metabolism in man. Journal of Clinical Investigation 49: 1266–1279 (1970).PubMedCrossRefGoogle Scholar
  100. Latham, A.N.; Turner, P.; Franklin, C. and Maclay, W.: Phenobarbitone-induced urinary excretion of D-glucaric acid and 6β-hydroxycortisol in man. Canadian Journal of Physiology and Pharmacology 54: 778–782 (1976).PubMedCrossRefGoogle Scholar
  101. Lewis, R.J.; Trager, W.F.; Chan, K.K.; Breckenridge, A.; Orme, M.L’E.; Rowland, M. and Schary, W.: Warfarin. Stereochemical aspects of its metabolism and the interaction with Phenylbutazone. Journal of Clinical Investigation 53: 1607–1617 (1974).PubMedCrossRefGoogle Scholar
  102. MacDonald, M.G. and Robinson, D.S.: Clinical observations of possible barbiturate interference with anticoagulation. Journal of the American Medical Association 204: 97–100 (1968).PubMedCrossRefGoogle Scholar
  103. Marsh, C.A.: Metabolism of D-glucuronolactone in mammalian systems: Identification of D-glucaric acid as a normal constituent of urine. Biochemical Journal 86: 77–86 (1963).PubMedGoogle Scholar
  104. Maxwell, J.D.; Hunter, J.; Stewart, D.A. and Williams, R.: Folate deficiency after anticonvulsant drugs: An effect of hepatic enzyme induction?. British Medical Journal 1: 297–299 (1972).PubMedCrossRefGoogle Scholar
  105. Meynell, M.J.: Megaloblastic anaemia in anticonvulsant therapy. Lancet 1: 487 (1966).PubMedCrossRefGoogle Scholar
  106. Michot, F.; Burgi, M. and Buttner, J.: Rimactan (Rifampizin) und Antikoagulantientherapie. Schweizerische Medizinische Wochenschrift 100: 583–584 (1970).PubMedGoogle Scholar
  107. Miguet, J.P.; Mavier, P.; Soussy, C.J. and Dhumeaux, D.: Induction of hepatic microsomal enzymes after brief administration of rifampicin in man. Gastroenterology 72: 924–926 (1977).PubMedGoogle Scholar
  108. Mitchell, J.R.; Potter, W.Z.; Hinson, J.A.; Snodgrass, R. and Gillette, J.R.: In Gillette (Ed) Concepts in Biochemical Pharmacology, p.383 (Springer-Verlag, New York 1975).CrossRefGoogle Scholar
  109. Morgan, D.P. and Roan, C.C.: Liver function in workers having high tissue stores of chlorinated hydrocarbon pesticides. Archives of Environmental Health 29: 14–17 (1974).PubMedGoogle Scholar
  110. Mountain, K.R.; Hirsh, J. and Gallus, A.S.: Neonatal coagulation defect due to anticonvulsant drug treatment in pregnancy. Lancet 1: 265–268 (1970).PubMedCrossRefGoogle Scholar
  111. Mowat, A.P.: Developmental effects on liver D-glucuronolactone dehydrogenase levels and on D-glucaric acid excretion in urine: Hormonal effects on D-glucaric acid excretion in urine. Journal of Endocrinology 42: 585–590 (1968).PubMedCrossRefGoogle Scholar
  112. Nayak, R.K.; Smith, R.D., Chamberlain, J.H.; Polk, A.; De Long, A.F.; Herezeg, T.; Chemburkar, P.B.; Hoslin, R.S. and Reavey-Cantnell, N.H.: Methaqualone pharmacokinetics after single- and multiple-dose administration in man. Journal of Pharmacokinetics and Biopharmaceutics 2: 107–121 (1974).PubMedCrossRefGoogle Scholar
  113. Nelson, S.D.; Mitchell, J.R.; Dybing, E. and Sasame, H.A.: Cytochrome P-450 mediated oxidation of 2-hydroxyestrogens to reactive intermediates. Biochemical and Biophysical Research Communications 70: 1157–1165 (1976).PubMedCrossRefGoogle Scholar
  114. Neuvonen, P.J. and Pentilla, O.: Interaction between doxycycline and barbiturates, British Medical Journal 1: 535–536 (1974).PubMedCrossRefGoogle Scholar
  115. Nocke-Fink, L.; Breuer, H. and Reimers, D.: Rifampicin auf den Menstruationszyklus und die Ostrogenausschiedung bei Einnahme oraler Kontrazeptiva. Deutsche Medizinische Wochenschrift 98: 1521–1523 (1973).CrossRefGoogle Scholar
  116. Ohnhaus, E.E. and Burgi, H.: The effect of three different enzyme inducing agents and their influence on thyroid hormone metabolism in man. European Journal of Clinical Investigation 8: 330 (1978).Google Scholar
  117. Ohnhaus, E.E. and Park, B.K.: Measurement of urinary 6-β-hydroxycortisol excretion as an in vivo parameter in the clinical assessment of the microsomal enzyme-inducing capacity of antipyrinc, phcnobarbitone and rifampicin. European Journal of Clinical Pharmacology 15: 139–145 (1979).PubMedCrossRefGoogle Scholar
  118. Ohnhaus, E.E.; Park, B.K.; Colombo, J.P. and Heizmann, P.: The effect of enzyme induction on diazepam metabolism in man. British Journal of Clinical Pharmacology 8: 557–563 (1979).PubMedCrossRefGoogle Scholar
  119. O’Malley, K.; Stevenson, I.H. and Crooks, J.: Impairment of human drug metabolism by oral contraceptive steroids. Clinical Pharmacology and Therapeutics 13: 552–557 (1972).PubMedGoogle Scholar
  120. O’Malley, K.; Sawyer, P.R. and Stevenson, I.H.: Effects of tricyclic antidepressants on drug metabolism. British Journal of Pharmacology 44: 372P–373P (1973).Google Scholar
  121. O’Malley, K.; Browning, M.; Stevenson, I.H. and Turnbull, M.J.: Stimulation of drug metabolism in man by tricyclic antidepressants. European Journal of Clinical Pharmacology 6: 102–106 (1973).PubMedCrossRefGoogle Scholar
  122. O’Reilly, R.A.: Interactions of sodium warfarin and rifampicin. Studies in man. Annals of Internal Medicine 81: 337–340 (1974).PubMedGoogle Scholar
  123. Orlowski, M.: The role of gamma-gluiamyl transpeptidase in the internal diseases clinic. Archivum Immunoliae et Therapiae Experimentalis 11: 1–16 (1963).Google Scholar
  124. Pantuck, E.J.; Hoiao, K-C.; Maggio, A.; Nakamura, K.; Kuntzman, R. and Conney, A.H.: Effect of smoking on phenacetin metabolism. Clinical Pharmacology and Therapeutics 15:9–16 (1974).PubMedGoogle Scholar
  125. Pantuck, E.J.; Pantuck, C.B.; Garland, W.A.; Mins, B.H.; Wattenberg, L.W.; Anderson, K.E.; Kappas, A. and Conney, A.H.: Stimulatory effect of brussel sprouts and cabbage on human drug metabolism. Clinical Pharmacology and Therapeutics 25: 88–95 (1979).PubMedGoogle Scholar
  126. Park, B.K.: A specific radioimmunoassay for 6β hydroxy-cortisol in human. Journal of Steroid Biochemistry 9: 963–966 (1978).PubMedCrossRefGoogle Scholar
  127. Park, B.K.; Whittaker, A.D. and Challiner, M.: The effect of enzyme induction on the irreversible binding of ethynyloestradiol to guinea pig liver microsomes. Life Sciences 23: 2463–2467 (1978).PubMedCrossRefGoogle Scholar
  128. Parke, D.V.: Enzyme Induction, pp.207–272 (Plenum Press, London 1975).Google Scholar
  129. Penttila, O.; Neuvonen, P.J.; Aho, K. and Lehtovaara, R.: Interaction between doxycycline and antiepileptic drugs. British Medical Journal 2: 470–472 (1974).PubMedCrossRefGoogle Scholar
  130. Peters, U.; Hauseman, T.U. and Grosse-Brockhoff, F.: Einfluss von Tuberkulostatika auf die Pharmakokinetik des Digitoxins. Deutsche Medizinische Wochenschrift 99: 2381–2386 (1974).PubMedCrossRefGoogle Scholar
  131. Petruch, F.; Schuppel, R.V.A. and Steinhilber, G.: Effect of diphenylhydantoin on hepatic drug hydroxylation. European Journal of Clinical Pharmacology 7: 281–285 (1974).PubMedCrossRefGoogle Scholar
  132. Pirttiaho, H.I.; Sontaniemi, E.A.; Ahokas, J.T. and Pitkanen, U.: Liver size and indices of drug metabolism in epileptics. British Journal of Clinical Pharmacology 6: 273–278 (1978).PubMedCrossRefGoogle Scholar
  133. Pitot, H.C.: In Estabrook and Lindenlaub (Eds) The Induction of Drug Metabolism, pp.472–483. Symposia Medica Hoechst 14 (Schattaner, New York 1979).Google Scholar
  134. Poland, A.; Smith, D.; Kuntzman, R.; Jacobson, M. and Conney, A.H.: Effect of intensive occupational exposure to DDT on Phenylbutazone and cortisol metabolism in human subjects. Clinical Pharmacology and Therapeutics 11: 724–729 (1970).PubMedGoogle Scholar
  135. Remmer, H.: In Ciba Foundation Symposium on Enzymes and Drug Action, p.276 (Little Brown, Boston 1962).Google Scholar
  136. Robinson, D.S. and MacDonald, M.S.: The effect of Phenobarbital administration on the control of coagulation achieved during Warfarin therapy in man. Journal of Pharmacology and Experimental Therapeutics 153: 250–253 (1976).Google Scholar
  137. Rosalki, S.B. and Rau, D.: Serum γ-glutamyl transpeptidase activity in alcoholism. Clinica Chimica Acta 39: 41–47 (1972).CrossRefGoogle Scholar
  138. Rosalki, S.B.; Tarlow, D. and Rau, D.: Plasma gamma-glutamyl transpeptidase elevation in patients receiving enzyme inducing drugs. Lancet 2: 376–377 (1971).PubMedCrossRefGoogle Scholar
  139. Rowland, M.: In Teorell, Dedrick and Condlitte (Eds) Pharmacology and Pharmacokinetics, p.321 (Plenum Press, London 1975).Google Scholar
  140. Rubin, E.; Gang, H.; Misra, P.S. and Lieber, C.S.: Inhibition of drug metabolism by acute ethanol intoxication. American Journal of Medicine 49: 801–806 (1970).PubMedCrossRefGoogle Scholar
  141. Rundles, R.W.; Wyngaarden, J.B.; Hitchings, G.H. and Ellon, G.B.: Drugs and uric acid. Annual Review of Pharmacology 9: 345–362 (1969).PubMedCrossRefGoogle Scholar
  142. Saggers, V.H.; Hariratnajothi, N. and McClean, A.E.M.: The effect of diet and phenobarbitone on Quinine metabolism in the rat and in man. Biochemical Pharmacology 19: 499–503 (1970).PubMedCrossRefGoogle Scholar
  143. Schmid, K.; Cornu, F.; Imhof, P. and Keberle, H.: Die biochemische Deutung der Gewöhnung an Schlafmittel. Schweizerische Medizinische Wochenschrift 94: 235–240 (1964).PubMedGoogle Scholar
  144. Serlin, M.J.; Sibeon, R.G.; Mossman, S.; Breckenridge, A.M.; Williams, J.B.B.; Atwood, J.L. and Willoughby, J.M.T.: Cimetidine: Interaction with oral anticoagulants. Lancet 2: 317–319 (1979).PubMedCrossRefGoogle Scholar
  145. Serlin, M.J.; Challiner, M.; Park, B.K.; Turcan, P.A. and Breckenridge, A.M.: Cimetidine potentiates the anticoagulant effect of warfarin by inhibition of drug metabolism. Biochemical Pharmacology 29: 1971–1972 (1980).PubMedCrossRefGoogle Scholar
  146. Sharpe, G.; Bell, G.D.; Cartwright, S.T.; Chaplin, S. and Henry, D.A.: Failure of 2h (14C)-aminopyrine breath test to demonstrate microsomal enzyme induction by glutethimide. British Journal of Clinical Pharmacology 5: 460P (1978).CrossRefGoogle Scholar
  147. Sjoqvist, F.: Psychotropic drugs (2). Interaction between monoamine oxidase (MAO) inhibitors and other substances. Proceedings of the Royal Society of Medicine 58: (Suppl.) 967–978 (1965).PubMedGoogle Scholar
  148. Sjoqvist, F. and von Bahr, C.: Interindividual differences in drug oxidation clinical importance. Drug Metabolism and Disposition 1: 469–482 (1973).PubMedGoogle Scholar
  149. Solomon, H.M. and Abrams, W.B.: Interaction between digitoxin and other drugs in man. American Heart Journal 83: 277–280 (1972).PubMedCrossRefGoogle Scholar
  150. 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 Sciences 179: 362–369 (1971).PubMedCrossRefGoogle Scholar
  151. Southern, A.L.; Gordon, G.G.; Tochimoto, S.; Krikun, E.; Kreiger, D.; Jacobson, M. and Kuntzman, R.: Effect of N-phenylbarbital (Phetharbital) on the metabolism of testosterone and cortisol in man. Journal of Clinical Endocrinology 29: 251–256 (1969).CrossRefGoogle Scholar
  152. Stevenson, I.H.: Factors influencing antipyrine elimination. British Journal of Clinical Pharmacology 4: 261–265 (1977).PubMedCrossRefGoogle Scholar
  153. Syvalahti, E.K.G.; Pihlajamaki, K.K. and Iisalo, E.J.: Rifampicin and drug metabolism. Lancet 2: 232–233 (1974).PubMedCrossRefGoogle Scholar
  154. Szewczuk, A.: A soluble form of gama-glutamyl transpeptidase in human tissues. Clinica Chimica Acta 14: 608–614 (1966).CrossRefGoogle Scholar
  155. Thomas, R.C. and Ikeda, C.J.: The metabolic fate of tolbutamide in man and in the rat. Journal of Medicinal Chemistry 9: 507–510 (1966).PubMedCrossRefGoogle Scholar
  156. van Dam, F.E. and Gribnau-Overkamp, M.J.H.: The effect of some sedatives (phenobarbital, glutethemide, chlordiazepoxide, chloral hydrate) on the rate of disappearance of ethyl biscoumacetate from the plasma. Folia Medicine Neerland 10: 141–145 (1967).Google Scholar
  157. Vesell, E.S.: The antipyrine test in clinical pharmacology: Conceptions and misconceptions. Clinical Pharmacology and Therapeutics 26: 275–286 (1979).PubMedGoogle Scholar
  158. Vesell, E.S. and Page, J.G.: Genetic control of the phenobarbitolinduced shortening of plasma antipyrine half-lives in man. Journal of Clinical Investigation 48: 2202–2209 (1969).PubMedCrossRefGoogle Scholar
  159. Vesell, E.S. and Passananti, G.T.: Inhibition of drug metabolism in man. Drug Metabolism and Disposition 1: 402–410 (1973).PubMedGoogle Scholar
  160. Vestal, R.E. and Wood, A.J.J.: Influence of age and smoking on drug kinetics in man. Studies using model compounds. Clinical Pharmacokinetics 5: 309–319 (1980).PubMedCrossRefGoogle Scholar
  161. Viala, A.; Cano, J.P.; Dranet, C; Tassinarai, C.A. and Roger, J.: Blood levels of diazepam (Valium) and N-desmethyl diazepam in the epileptic child. A preliminary report. Psychiatric Neurologie Neuroschire 74: 153–158 (1971).Google Scholar
  162. Videla, L; Bernstein, J. and Israel, Y.: Metabolic alterations produced in the liver by chronic ethanol administration. Bio-Chemical Journal 134: 507–514 (1973).Google Scholar
  163. Wagner, J.G.; Northam, J.I.; Alway, C.D. and Carpenter, O.S.: Blood levels of drug at the equilibrium state after multiple dosing. Nature (London) 207: 1301–1302 (1965).CrossRefGoogle Scholar
  164. Wagstaff, D.J. and Short, C.R.: Induction of hepatic microsomal hydroxylating enzymes by technical piperonylbutoxide and some of its analogs. Toxicology and Applied Pharmacology 19: 54–61 (1971).PubMedCrossRefGoogle Scholar
  165. Werk, E.E.; MacGee, J. and Sholiton, L.J.: Effect of diphenylhydantoin on cortisol metabolism in man. Journal of Clinical Investigation 43: 1824–1834 (1964).PubMedCrossRefGoogle Scholar
  166. Werk, E.E.; Thrasher, K.; Sholiton, L.J.; Olinger, C. and Choi, Y.: Cortisol production in epileptic patients treated with diphenylhydantoin. Clinical Pharmacology and Therapeutics 12: 698–703 (1971).PubMedGoogle Scholar
  167. Whitfield, J.B.; Moss, D.W.; Neale, G.; Orme, M.L’E. and Breckenridge, A.: Changes in plasma γ-glutamyl transpeptidase activity associated with alterations in drug metabolism in man. British Medical Journal 1: 316–318 (1973).PubMedCrossRefGoogle Scholar
  168. Whittaker, J.A. and Price-Evans, D.A.: Genetic control of Phenylbutazone metabolism in man. British Medical Journal 4: 323–328 (1970).PubMedCrossRefGoogle Scholar
  169. Wilkinson, C.F.; Hetnarski, K. and Hicks, L.J.: Substituted imidazoles as inhibitors of microsomal oxidation and insecticide synergists. Pesticide Biochemistry and Physiology 4: 299–312 (1974).CrossRefGoogle Scholar
  170. Wilkinson, G.R. and Shand, D.G.: A physiological approach to hepatic drug clearance. Clinical and Experimental Therapeutics 18: 377–390 (1975).Google Scholar
  171. Williams, R.T.: Inter-species variations in the metabolism of xenobiotics: Biochemical Society Transactions 2: 369–377 (1974).Google Scholar
  172. Yamaji, T.; Motohashi, K.; Murakawa, S. and Ibayashi, H.; Urinary excretion of 6β-hydroxycortisol in states of altered thyroid function. Journal of Clinical Endocrinology and Metabolism 29: 801–806 (1969).PubMedCrossRefGoogle Scholar
  173. Yates, M.S.; Hiley, C.R.; Roberts, P.J.; Back, D.J. and Crawford, F.E.: Differential effects of hepatic microsomal enzyme inducing agents on liver blood flow. Biochemical Pharmacology 27: 2617–2621 (1978).PubMedCrossRefGoogle Scholar
  174. Yates, M.S.; Hiley, C.R.; Chaliiner, M.R. and Park, B.K.: Phenobarbitone effects on hepatic microsomal enzymes and liver blood flow in the guinea pig. Biochemical Pharmacology 28: 2856–2857 (1979).PubMedCrossRefGoogle Scholar
  175. Zilly, W.; Breimer, D.D. and Richter, E.: Induction of drug metabolism in man after rifampicin treatment measured by increased hexobarbital and tolbutamide clearance. European Journal of Clinical Pharmacology 9: 219–227 (1975).PubMedCrossRefGoogle Scholar

Copyright information

© ADIS Press Australasia Pty Ltd 1981

Authors and Affiliations

  • B. K. Park
    • 1
  • A. M. Breckenridge
    • 1
  1. 1.Department of Pharmacology and TherapeuticsUniversity of LiverpoolLiverpoolEngland

Personalised recommendations