Pharmacokinetics and enterohepatic circulation of (E)-2-ene valproic acid in the rat.

A pharmacologically active monounsaturated metabolite of valproic acid (VPA), (E)-2-ene VPA, was administered by an intravenous bolus dose of 20 mg/kg to normal and bile-exteriorized rats. The total plasma clearance of (E)-2-ene VPA in normal rats was 4.9 ml/min/kg and in bile-exteriorized rats, 7.7 ml/min/kg. (E)-2-ene was recycled in the plasma of normal rats due to enterohepatic circulation. Approximately 32% of the dose was excreted in the urine of normal rats. Of the administered dose to bile exteriorized rats, approximately 27% was excreted in the urine and 38% in the bile. Administration of (E)-2-ene increased bile flow rate, and the induced choleresis lasted for 3-4 h. (E)-2-ene VPA was largely excreted in apparently conjugated form in the urine and bile. The pharmacokinetics of (E)-2-ene VPA were similar to that of the parent drug VPA.