Title: THE EFFECT OF ANTICONVULSANT DRUGS WHICH INDUCE LIVER MICROSOMAL ENZYMES ON DERIVED AND INGESTED PHENOBARBITONE LEVELS
Abstract: Acta Neurologica ScandinavicaVolume 56, Issue 1 p. 1-6 THE EFFECT OF ANTICONVULSANT DRUGS WHICH INDUCE LIVER MICROSOMAL ENZYMES ON DERIVED AND INGESTED PHENOBARBITONE LEVELS Noel Callaghan, Noel Callaghan Departments of Neurology & Biochemistry, St. Finbarr's Hospital, Cork, Ireland, and Mathematical Analysis Section, Ciba-Geigy Pharmaceuticals, Simonsway, Manchester.Search for more papers by this authorMorgan Feely, Morgan Feely Departments of Neurology & Biochemistry, St. Finbarr's Hospital, Cork, Ireland, and Mathematical Analysis Section, Ciba-Geigy Pharmaceuticals, Simonsway, Manchester.Search for more papers by this authorFinbar Duggan, Finbar Duggan Departments of Neurology & Biochemistry, St. Finbarr's Hospital, Cork, Ireland, and Mathematical Analysis Section, Ciba-Geigy Pharmaceuticals, Simonsway, Manchester.Search for more papers by this authorMichael O'callaghan, Corresponding Author Michael O'callaghan Departments of Neurology & Biochemistry, St. Finbarr's Hospital, Cork, Ireland, and Mathematical Analysis Section, Ciba-Geigy Pharmaceuticals, Simonsway, Manchester.N. Callaghan, M.D., Department of Neurology, St. Finbarr s Hospital, Cork, IrelandSearch for more papers by this authorJ. Seldrup, J. Seldrup Departments of Neurology & Biochemistry, St. Finbarr's Hospital, Cork, Ireland, and Mathematical Analysis Section, Ciba-Geigy Pharmaceuticals, Simonsway, Manchester.Search for more papers by this author Noel Callaghan, Noel Callaghan Departments of Neurology & Biochemistry, St. Finbarr's Hospital, Cork, Ireland, and Mathematical Analysis Section, Ciba-Geigy Pharmaceuticals, Simonsway, Manchester.Search for more papers by this authorMorgan Feely, Morgan Feely Departments of Neurology & Biochemistry, St. Finbarr's Hospital, Cork, Ireland, and Mathematical Analysis Section, Ciba-Geigy Pharmaceuticals, Simonsway, Manchester.Search for more papers by this authorFinbar Duggan, Finbar Duggan Departments of Neurology & Biochemistry, St. Finbarr's Hospital, Cork, Ireland, and Mathematical Analysis Section, Ciba-Geigy Pharmaceuticals, Simonsway, Manchester.Search for more papers by this authorMichael O'callaghan, Corresponding Author Michael O'callaghan Departments of Neurology & Biochemistry, St. Finbarr's Hospital, Cork, Ireland, and Mathematical Analysis Section, Ciba-Geigy Pharmaceuticals, Simonsway, Manchester.N. Callaghan, M.D., Department of Neurology, St. Finbarr s Hospital, Cork, IrelandSearch for more papers by this authorJ. Seldrup, J. Seldrup Departments of Neurology & Biochemistry, St. Finbarr's Hospital, Cork, Ireland, and Mathematical Analysis Section, Ciba-Geigy Pharmaceuticals, Simonsway, Manchester.Search for more papers by this author First published: July 1977 https://doi.org/10.1111/j.1600-0404.1977.tb01403.xCitations: 8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL ABSTRACT A comparison was made between the levels of derived Phenobarbitone in three groups of patients who were taking Primidone as a single drug, Primidone with Phenytoin and Primidone in combination with Phenytoin and Carbamazepine. The levels of ingested Phenobarbitone when this drug was taken as a single drug were compared with the levels when Phenobarbitone was taken in combination with Phenytoin in two other groups of patients. A significant increase in derived Phenobarbitone levels occurred when Primidone was used in combination with Phenytoin alone or with Phenytoin and Carbamazepine. The highest level occurred in a group of patients taking the three drug combination. There was no significant difference between the levels of ingested Phenobarbitone when this drug was used as single therapy or in combination with Phenytoin. We suggest that the increase in derived Phenobarbitone levels relates to the effect of Phenytoin on liver enzyme systems, and that the greater increase with triple therapy was related to the combined effect of Carbamazepine and Phenytoin on microsomal enzymes. As there was no increase in ingested Phenobarbitone levels when this drug was taken in combination with Phenytoin, we were unable to confirm previous suggestions that Phenytoin either inhibits the hydroxylation of Phenobarbitone or impairs its renal excretion. References Dunn, O. J. 1964: Multiple Comparisons using Ranks Sums. Technometrics. 6, 241– 252. Eadie, J. J, &, Tyrer, J. H 1974: Anticonvulsant Therapy: Pharmacological Basis. and Practice. p. 95– 98. Churchill Livingstone, Edinburgh and London . Fincham, R. W., D. Schottelius, &, A. L Sahs 1974: The Influence of Diphenyl-hydantoin. on Primidone Metabolism. Arch. Neurol. 30, 259– 262. Kruskal, W. H, &, W. A. Wallis 1952: Use of Ranks in One-Criterion Variance. Analysis. J. Amer. Statist. Anns. 47, 583– 621. Morselli, P. L., M. Rizzo, &, S Garattini 1971: Interaction between Phenobarbitol. and Diphenylhydantoin in Animals and in Epileptic Patients. Ann. N. Y. Acad. Sci. 197, 88– 107. Morselli, P. L., P Biandrate, A Frigerio, &, S Garattini 1962: Pharmakinetics of. Carbamazepine in Rats and Humans. Europ. J. Clin. Invest. 2, 297– 300. Olesen, O. V, &, M. Dam 1967: The Metabolic Conversion of Primidone (Mysoline).to Phenobarbitone in patients having long-term treatment. Acta Neurol. scand. 43, 348– 356. Reynolds, E. H., G. Fenton, P. Fenwick, A. L. Johnson, &, M Laundy 1975: Interaction. of Phenytoin and Primidone. Brit. Med. J. 2, 594– 595. Rizzo, M., P. L. Morselli, &, S Garattini 1971: Further Observations on the Interactions. between Phenobarbital and Diphenylhydantoin during clinical treatment. in the rat. Biochemical Pharmacology 18, 449– 454. Roger, J. C., G. Rodgers, &, A. Soo 1973: Simultaneous determination of Carbamazepine. (Tegretol) and other Anticonvulsants in human plasma by Gas. Liquid Chromatography. Clin. Chem. 19, p. 590. Citing Literature Volume56, Issue1July 1977Pages 1-6 ReferencesRelatedInformation