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

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. 1992 The British Pharmacological Society