Summary
The pharmacokinetics of orally administered cimetidine was studied in 8 healthy subjects before and after 3 weeks of treatment with phenobarbital 100 mg daily, and in a separate study 4 subjects received cimetidine intravenously before and after the administration of phenobarbital. There was no change in the volume of distribution, but total plasma clearance was increased by a mean of 18%, mainly due to a 37% increase in nonrenal clearance. Renal clearance and half-life were not significantly altered. The area under the plasma concentration-time curve after oral administration was significantly (P≪0.05) reduced by a mean of 15% after phenobarbital treatment. The amount of cimetidine excreted in urine and its sulphoxide metabolite were significantly (P<0.05) reduced, on average by 34% and 26%, respectively by phenobarbital treatment. The data indicate that an apparent 20% reduction in the absorption of cimetidine was due to induction of gastrointestinal metabolism of cimetidine, with some contribution also from hepatic metabolism. Reduced absorption per se could not be totally excluded. Although the magnitude of the change was small, the finding of an 11% decrease in the time to achieve an effective plasma level of cimetidine after phenobarbital treatment may contribute to the ineffectiveness of cimetidine in certain patients.
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References
Somogyi A, Rohner H-G, Gugler R (1980) Pharmacokinetics and bioavailability of cimetidine in gastric and duodenal ulcer patients. Clin Pharmacokinet 5: 84–94
Redolfi A, Borgogelli E, Lodola E (1979) Blood level of cimetidine in relation to age. Eur J Clin Pharmacol 15: 257–261
Somogyi A, Gugler R (1980) Age dependent kinetics of cimetidine. World Conference of Clinical Pharmacology and Therapeutics, London, 3–9 August. Abstract No. 0735
Walkenstein SS, Dubb JW, Randolph WC, Westlake WJ, Stote RM, Intoccia AP (1978) Bioavailability of cimetidine in man. Gastroenterology 74: 360–365
Grahnén A, von Bahr C, Lindström B, Rosén A (1979) Bioavailability and pharmacokinetics of cimetidine. Eur J Clin Pharmacol 16: 335–340
Somogyi A (1980) Unpublished findings
Taylor DC, Cresswell PR, Bartlett DC (1978) The metabolism and elimination of cimetidine, a histamine H2-receptor antagonist, in the rat, dog, and in man. Drug Metab Dispos 6: 21–30
Serlin MJ, Sibeon RG, Mossman S, Breckenridge AM, Williams JRB, Atwood JL, Willoughby JMT (1979) Cimetidine: Interaction with oral anticoagulants in man. Lancet 2: 317–319
Klotz U, Reimann I (1980) Delayed clearance of diazepam due to cimetidine. N Engl J Med 302: 1012–1014
Randolph WC, Osborne WL, Walkenstein S, Intoccia AP (1977) High-pressure liquid chromatographic analysis of cimetidine, a histamine H2-receptor antagonist, in blood and urine. J Pharm Sci 66: 1148–1150
Cohen IA, Siepler JK, Nation R, Bombeck CT, Nyhus LM (1980) Relationship between cimetidine plasma levels and gastric acidity in acutelly ill patients. Am J Hosp Pharm 37: 375–379
Sedman AJ, Wagner JG (1974) AUTOAN — a decision-making pharmacokinetic computer program. Publication Distribution Service, Ann Arbor
Boxenbaum HG, Riegelman S, Elashoff RM (1974) Statistical estimations in pharmacokinetics. J Pharmacokinet Biopharm 2: 123–148
Wagner JG (1976) Linear pharmacokinetic equations allowing direct calculation of many needed pharmacokinetic parameters from the coefficients and exponents of the polyexponential equations which have been fitted to the data. J Pharmacokinet Biopharm 4: 443–467
Daniel WW (1978) Applied Nonparametric Statistics. Houghton Mifflin, Boston, pp 135–139
Hvidberg EF, Dam M (1976) Clinical pharmacokinetics of anticonvulsants. Clin Pharmacokinet 1: 161–188
Ohnhaus EE, Martin J, Kinser J, Colombo JP (1977) Enzyme induction and renal function in man. Br J Clin Pharmacol 4: 33–37
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Somogyi, A., Thielscher, S. & Gugler, R. Influence of phenobarbital treatment on cimetidine kinetics. Eur J Clin Pharmacol 19, 343–347 (1981). https://doi.org/10.1007/BF00544584
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DOI: https://doi.org/10.1007/BF00544584