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 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.
Pisani
F
F
Institute of Neurological and Neurosurgical Sciences, University of Messina, Italy.
Fazio
A
A
Artesi
C
C
Oteri
G
G
Spina
E
E
Tomson
T
T
Perucca
E
E
D000284:Administration, Oral; D000328:Adult; D000577:Amides / Q000494:pharmacology*; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged
D000577:Amides; D014151:Anti-Anxiety Agents; D002220:Carbamazepine; C045179:valnoctamide; C012227:carbamazepine epoxide