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

Abstract

Abstract. This 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 μg/ml. Peak levels were reached 3.5 hours after drug intake, the mean peak plasma CPIB concentration being 193 μg/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 μg/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.