TY - JOUR T1 - Metabolic fate of valproic acid in the rhesus monkey. Formation of a toxic metabolite, 2-n-propyl-4-pentenoic acid. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 443 LP - 453 VL - 14 IS - 4 AU - A W Rettenmeier AU - W P Gordon AU - K S Prickett AU - R H Levy AU - J S Lockard AU - K E Thummel AU - T A Baillie Y1 - 1986/07/01 UR - http://dmd.aspetjournals.org/content/14/4/443.abstract N2 - The metabolic fate of an iv bolus dose (13.5 mg kg-1) of valproic acid (VPA) was studied in adult male rhesus monkeys. Renal excretion proved to be the major route of elimination of the drug and a total of 17 metabolites, accounting collectively for some 82% of the administered dose, were identified in urine by GC-MS techniques. Many of these metabolites were present largely in the form of glucuronide conjugates, as was VPA itself. The principal pathways of VPA biotransformation were, in order of decreasing quantitative importance, ester glucuronide formation, omega-oxidation, beta-oxidation and (omega-1)-hydroxylation. In addition, three mono-unsaturated metabolites, identified as (E)-delta 2-, (E)-delta 3-, and delta 4-VPA, were detected in both plasma and urine. Quantitative analysis of these unsaturated VPA metabolites indicated that the delta 4 olefin, which is known to be a potent hepatotoxic agent, was the predominant isomer of the group. ER -