Impairment of carbamazepine-10, 11-epoxide elimination by valnoctamide, a valpromide isomer, in healthy subjects

Br J Clin Pharmacol. 1992 Jul;34(1):85-7. doi: 10.1111/j.1365-2125.1992.tb04114.x.

Abstract

The effect of the valpromide isomer valnoctamide (VCD, 200 mg three times daily for 8 days), an over-the-counter tranquillizer, on the elimination kinetics of a single oral dose of carbamazepine-10, 11-epoxide (CBZ-E, 100 mg) was investigated in healthy subjects. During VCD treatment, the half-life of CBZ-E was prolonged significantly compared with control (19.7 +/- 6.7 h vs 6.9 +/- 2.0 h, means +/- s.d., P less than 0.01), and its oral clearance decreased four-fold (from 109.6 +/- 30.7 to 28.8 +/- 11.1 ml h-1 kg-1, P less than 0.01). These findings indicate that VCM, like valpromide, strongly inhibits epoxide hydrolase in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Amides / pharmacology*
  • Anti-Anxiety Agents / pharmacology*
  • Carbamazepine / analogs & derivatives*
  • Carbamazepine / blood
  • Carbamazepine / pharmacokinetics
  • Drug Interactions
  • Female
  • Half-Life
  • Humans
  • Male
  • Middle Aged

Substances

  • Amides
  • Anti-Anxiety Agents
  • Carbamazepine
  • valnoctamide
  • carbamazepine epoxide