THE METABOLIC-FATE OF STIRIPENTOL IN MAN

  • 1 November 1986
    • journal article
    • research article
    • Vol. 14  (6) , 654-662
Abstract
The metabolism of stiripentol (I), a new antiepileptic drug, was studied in healthy human subjects. Following a single 1200-mg oral dose to one subject, 13 metabolites of I were detected in urine and were identified by GC/MS techniques. The structures of 9 of these metabolites were confirmed subsequently by synthesis of the corresponding reference compounds. The nature of the urinary metabolites of I revealed the operation of five distinct metabolic pathways for this drug, viz. 1) conjugation with glucuronic acid, 2) oxidative cleavage of the methylenedioxy ring system, 3) O-methylation of catechol metabolites, 4) hydroxylation of the t-butyl group, and 5) conversion of the allylic alcohol side-chain to the isomeric 3-pentanone structure. Metabolites of I excreted into urine over 12 hr accounted for the majority (73%) of an acute dose, whereas a further 18% was recovered in feces as the unchanged drug. These findings suggested that the search for additional metabolites would yield only trace amounts. From a quantitative standpoint, the most important pathway of biotransformation of I following both acute and chronic dosing involved opening of the methylenedioxy ring to generate catechol derivatives. This finding probably accounts for the known inhibitor effects of I on the oxidative metabolism of other antiepileptic agents and for the clinically significant drug interactions involving stiripentol.

This publication has 1 reference indexed in Scilit: