Urinary excretion of valproate and some metabolites in chronically treated patients

Urinary excretion of the antiepileptic agent valproic acid (VPA) and major metabolites from its glucuronidation, beta-oxidation, and omega- and omega 1-hydroxylation pathways were studied under steady state conditions in 24 epileptic patients. Some 55 +/- 18% (SD) of the daily dose was recovered in urine, 33 +/- 14% in the form of VPA-glucuronide, 15 +/- 8% as beta-oxidation products, and 4 +/- 2% and 2 +/- 1% as products of the omega- and omega 1-hydroxylation pathways, respectively. Only 1 +/- 2% of the dose was excreted unchanged. The proportion metabolized by direct glucuronidation tended to increase with dose at the expense of the oxidative pathways, particularly beta-oxidation. However, the wide variation in the patterns of urinary metabolite excretion precludes use of routinely collected urinary excretion data as a basis for detecting any but severe noncomplicance with VPA therapy or abnormalities of VPA metabolism.