Urinary Excretion of Valproate and Some Metabolites in Chronically Treated Patients

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Abstract
Urinary excretion of the antiepileptic agent valproic acid (VPA) and major metabolites from its glucuronidation, β-oxidation, and ω- and ω1-hydroxylation pathways were studied under steady state conditions in 24 epileptic patients. Some 55 \pm 18% (SD) of the daily dose was recovered in urine, 33 \pm 14% in the form of VPA-glucuronide, 15 \pm 8% as β-oxidation products, and 4 \pm 2% and 2 \pm 1% as products of the ω- and ω1-hydroxylation pathways, respectively. Only 1 \pm 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 β-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 noncompliance with VPA therapy or abnormalities of VPA metabolism.