Lack of Effect of Cholestyramine on the Pharmacokinetics of Clofibrate in Man

Abstract

The study was undertaken to determine whether cholestyramine (16 g daily) interfered with clofibrate absorption when the two drugs were given together. Fifteen patients taking 1 g of clofibrate twice daily (for 2 to 416 weeks) participated in the study. Clofibrate (as the acid, p-chlorophenoxyisobutyric acid, CPIB) was quantified by thin-layer and gas-liquid chromatography. In patients taking clofibrate only, mean plasma CPIB concentration before the morning dose of clofibrate was 123 mug/ml. Peak levels were reached 3.5 hours after drug intake, the mean peak plasma CPIB concentration being 193 mug/ml. Absorption of CPIB exceeded 99%. Ninety-eight percent of the daily CPIB-intake was excreted in the urine, 61% being conjugated. In vivo degradation of CPIB did not occur. Free and conjugated CPIB was present in bile (mean fasting level being 55 mug/ml. The decay of radioactive CPIB in plasma was not log-linear: the mean t 1/2 of the first exponential was 0.45 hours, and of the second 15.1 hours. The pool size in 3 patients 3 hours after the morning dose of clofibrate was 1054 mg. CPIB was not detectable in adipose tissue, and kinetic data gave no hint of drug accumulation in patients on long-term therapy. In 6 patients given cholestyramine together with clofibrate, there was no significant alteration in fasting plasma CPIB levels, 24-hour urinary and faecal excretion of CPIB or in the half-life and pool size of the drug. A short delay in reaching peak plasma CPIB levels was the only consistent finding.