Pharmacokinetics of probucol in male rats

The bioavailability and pharmacokinetic behavior of 10 mg/kg of [14C]probucol in an oil-water emulsion was determined after oral and intravenous administration to rats. The bioavailability of the oral formulation was approximately 6%. For the first 12-h interval after the intravenous bolus, plasma probucol concentrations increased after an initial decrease. This effect may be attributed to the formulation or precipitation of the drug in the vasculature. The terminal plasma half-life was 6 d. By 7 d, 45 and 4.65% of the labeled intravenous bolus was excreted in the feces and in the urine, respectively. Although most of the labeled dose was excreted in the bile, any enterohepatic recirculation that did occur did not contribute to the atypical plasma concentration versus time profile. The tissue distribution of the label and elimination rates in the bile differed between the two routes of administration. Either the total body burden, precipitation of the drug, or the emulsion vehicle may be responsible for the nonlinear distribution and clearance of the intravenous dose.