Summary
The pharmacokinetics of carbamazepine (CBZ) were studied in 7 patients with duodenal ulcer both before and after 14 days’ treatment with omeprazole (20 mg/day), as this substituted benzimidazole has been shown to alter the pharmacokinetics of some drugs. CBZ serum levels were determined by high pressure liquid chromatography following oral administration of CBZ 400mg. Omeprazole treatment caused increases in CBZ blood levels and significantly prolonged the elimination half-life from 17.2 ± 5.9 hours to 37.3 ± 22.8 hours. Simultaneously, there was an increase in the area under the curve (AUC0-∞) from 382.3 ± 81.1 μg/ml · h to 668.8 ± 241.6 μg/ml · h, while the CBZ clearance was decreased significantly from 20.7 ± 3.4 ml/h/kg to 12.5 ± 3.5 ml/h/kg. Other parameters such as maximum plasma drug concentration (Cmax), time to reach maximum concentration (tmax), and apparent volume of distribution at steady-state (Vss) were, however, not altered by omeprazole treatment. The reduction in clearance and increase in half-life and AUC0-∞ values may be attributed to inhibition of CBZ oxidative metabolism by omeprazole.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andersson T. Omeprazole drug interaction studies. Clinical Pharmacokinetics 21: 195–212, 1991
Andersson T, Cederberg C, Edvardsson G, Heggelund A, Lyndborg P. Effect of omeprazole treatment on diazepam plasma levels in slow versus normal rapid metabolizers of omeprazole. Clinical Pharmacology and Therapeutics 47: 79–85, 1990
Andersson T, Regärdh CG, Dabl-Puustinen ML, Bertilsson L. Slow omeprazole metabolisers are also poor S-mephenytoin hydroxylators. Therapeutic Drug Monitoring 12: 415–416, 1990
Cohen AF, Kroon R, Schoemaker HC, Hoogmaker JWF, Vanvliet-Verbeck A. Effect of gastric acidity on the bioavailability of digoxin. Evidence of new mechanism for interaction with omeprazole. British Journal of Clinical Pharmacology 31: 565, 1991
Dickins M, Bridges JW. The relationship between the binding of 2-n-alkylbenzimidazole to rat hepatic microsomal cytochrome P-450 and the inhibition of monooxygenation. Biochemical Pharmacology 31: 1315–1320, 1982
Eichelbaum M, Tomson T, Tybring G, Bertilsson L. Carbamazepine metabolism in man: induction and pharmacogenetic aspects. Clinical Pharmacokinetics 10: 80–90, 1985
Grimsley SR, Jann MW, Carter JG, D’Mello AP, D’souza MJ. Increased carbamazepine plasma concentrations after fluoxetine co-administration. Clinical Pharmacology and Therapeutics 50: 10–15, 1991
Gugler R, Jensen JC. Omeprazole inhibits elimination of diazepam. Lancet 1: 969, 1984
Gugler R, Jensen JC. Omeprazole inhibits oxidative drug metabolism — studies with diazepam and phenytoin in vivo and 7-ethoxycoumarin in vitro. Gastroenterology 89: 1235–1241, 1985
Gugler R, Jensen JC. Drugs other than H2 receptor antagonist as clinically important inhibitors of drug metabolism in vivo. Pharmacology and Therapeutics 33: 133–137, 1987
Henry DA, Somerville KW, Kitchingman G, Langman MJS. Omeprazole: effect on oxidation drug metabolism. British Journal of Clinical Pharmacology 18: 195–200, 1984
Hetzel DJ, Bochner F, Hallpike JF, Shearman DJC, Hann CS. Cimetidine interaction with phenytoin. British Medical Journal 1: 1512, 1981
Jensen JC, Gugler R. Inhibition of human liver cytochrome P-450 by omeprazole. British Journal of Clinical Pharmacology 21: 328–330, 1986
Kabra PM, Stafford BE, Marton LJ. Simultaneous measurement of phenobarbital, phenytoin, primidone, ethosuximide, and carbamazepine in serum by high pressure liquid chromatography. Clinical Chemistry 23/7: 1284–1288, 1977
Klotz U, Reimann I. Delayed clearance of diazepam due to cimetidine. New England Journal of Medicine 302: 1012–1014, 1980
Larsson H, Carlsson E, Junggrend U, Olbe L, Sjostrand SE, et al. Inhibition of gastric acid secretion by omeprazole in the dog and rat. Gastroenterology 85: 900–907, 1983
Levy RH, Kerr BM. Clinical pharmacokinetics of carbamazepine. Journal of Clinical Psychiatry 49: 58–61, 1988
Oosterhuis B, Jonkman JHG, Andersson T, Zuiderwijk PBM, Jedema JN. Minor effects of multiple dose omeprazole on the pharmacokinetics of digoxin after a single oral dose. British Journal of Clinical Pharmacology 32: 569–572, 1991
Pearson HJ. Interaction of fluoxetine with carbamazepine (letter). Journal of Clinical Psychiatry 51: 126, 1990
Pippenger CE. Clinically significant carbamazepine drug interactions: an overview. Epilepsia 28: 571–576, 1987
Pisani F, Narbone MC, Fazio A, et al. Effect of Viloxazine on serum carbamazepine levels in epileptic patients. Epilepsia 25: 482–485, 1984
Somogyi A, Muirhead M. Pharmacokinetic interactions of cimetidine. Clinical Pharmacokinetics 12: 321–366, 1987
Soons PA, Vanderberg G, Danhof M, Brummelen PV, Jansen JBMJ, et al. Influence of single and multiple-dose omeprazole treatment on nifedipine pharmacokinetics and effects in healthy subjects. European Journal of Clinical Pharmacology 42: 319–324, 1992
Sutfin T, Balmer K, Bostrom H, Eriksson S, Hoglund P, et al. Stereoselective interaction of omeprazole with warfarin in healthy men. Therapeutic Drug Monitoring 12: 329–333, 1989
Tellerman-Toppet N, Duret ME, Loers C. Cimetidine interaction with carbamazepine. Annals of Internal Medicine 94: 544, 1981
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Naidu, M.U.R., Shobha, J.C., Dixit, V.K. et al. Effect of Multiple Dose Omeprazole on the Pharmacokinetics of Carbamazepine. Drug Invest 7, 8–12 (1994). https://doi.org/10.1007/BF03257393
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03257393