RT Journal Article SR Electronic 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 FD American Society for Pharmacology and Experimental Therapeutics SP 443 OP 453 VO 14 IS 4 A1 A W Rettenmeier A1 W P Gordon A1 K S Prickett A1 R H Levy A1 J S Lockard A1 K E Thummel A1 T A Baillie YR 1986 UL http://dmd.aspetjournals.org/content/14/4/443.abstract AB 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.