IMPAIRMENT OF CARBAMAZEPINE-10, 11-EPOXIDE ELIMINATION BY VALNOCTAMIDE, A VALPROMIDE ISOMER, IN HEALTHY-SUBJECTS

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 < 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 < 0.01). These findings indicate that VCM, like valpromide, strongly inhibits epoxide hydrolase in vivo.