Abstract
The pharmacokinetics and serum protein binding of oxazepam, a drug mainly eliminated by a single step glucuronidation reaction, were studied in nine epileptic patients treated long-term with phenytoin or phenytoin with phenobarbitone, and in nine healthy control subjects. Oxazepam elimination half-life was shorter and apparent oral clearance higher in treated patients than in age and sex matched control subjects. Serum bilirubin concentration was lower in treated patients. There was no significant correlation between serum bilirubin concentrations and oxazepam elimination. Serum alpha 1-acid glycoprotein concentration was higher in the treated patients than in the control group. Oxazepam was more than 93% bound to serum proteins, but the extent of binding was not significantly different between the two groups. These results show that oxazepam glucuronyl transferase activity is increased by treatment with phenytoin alone or in combination with phenobarbitone in epileptic patients.
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- Alván G., Piafsky K., Lind M., von Bahr C. Effect of pentobarbital on the disposition of alprenolol. Clin Pharmacol Ther. 1977 Sep;22(3):316–321. doi: 10.1002/cpt1977223316. [DOI] [PubMed] [Google Scholar]
- Black M., Perrett R. D., Carter A. E. Hepatic bilirubin UDP-glucuronyl transferase activity and cytochrome P450 content in a surgical population, and the effects of preoperative drug therapy. J Lab Clin Med. 1973 May;81(5):704–712. [PubMed] [Google Scholar]
- Branch R. A., Shand D. G., Wilkinson G. R., Nies A. S. Increased clearance of antipyrine and d-propranolol after phenobarbital treatment in the monkey. Relative contributions of enzyme induction and increased hepatic blood flow. J Clin Invest. 1974 Apr;53(4):1101–1107. doi: 10.1172/JCI107647. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenblatt D. J. Clinical pharmacokinetics of oxazepam and lorazepam. Clin Pharmacokinet. 1981 Mar-Apr;6(2):89–105. doi: 10.2165/00003088-198106020-00001. [DOI] [PubMed] [Google Scholar]
- Greenblatt D. J., Divoll M., Harmatz J. S., Shader R. I. Oxazepam kinetics: effects of age and sex. J Pharmacol Exp Ther. 1980 Oct;215(1):86–91. [PubMed] [Google Scholar]
- Müller W., Wollert U. Characterization of the binding of benzodiazepines to human serum albumin. Naunyn Schmiedebergs Arch Pharmacol. 1973;280(3):229–237. doi: 10.1007/BF00501348. [DOI] [PubMed] [Google Scholar]
- Patwardhan R. V., Yarborough G. W., Desmond P. V., Johnson R. F., Schenker S., Speeg K. V., Jr Cimetidine spares the glucuronidation of lorazepam and oxazepam. Gastroenterology. 1980 Nov;79(5 Pt 1):912–916. [PubMed] [Google Scholar]
- Routledge P. A., Stargel W. W., Finn A. L., Barchowsky A., Shand D. G. Lignocaine disposition in blood in epilepsy. Br J Clin Pharmacol. 1981 Nov;12(5):663–666. doi: 10.1111/j.1365-2125.1981.tb01286.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scott A. K., Jeffers T. A., Petrie J. C., Gilbert J. C. Serum bilirubin and hepatic enzyme induction. Br Med J. 1979 Aug 4;2(6185):310–310. doi: 10.1136/bmj.2.6185.310. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watkins J. B., Gregus Z., Thompson T. N., Klaassen C. D. Induction studies on the functional heterogeneity of rat liver UDP-glucuronosyltransferases. Toxicol Appl Pharmacol. 1982 Jul;64(3):439–446. doi: 10.1016/0041-008x(82)90240-x. [DOI] [PubMed] [Google Scholar]
- Whitfield J. B., Pounder R. E., Neale G., Moss D. W. Serum -glytamyl transpeptidase activity in liver disease. Gut. 1972 Sep;13(9):702–708. doi: 10.1136/gut.13.9.702. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilkinson G. R., Shand D. G. Commentary: a physiological approach to hepatic drug clearance. Clin Pharmacol Ther. 1975 Oct;18(4):377–390. doi: 10.1002/cpt1975184377. [DOI] [PubMed] [Google Scholar]