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Impairment of carbamazepine‐10, 11‐epoxide elimination by valnoctamide, a valpromide isomer, in healthy subjects.
Author(s) -
Pisani F,
Fazio A,
Artesi C,
Oteri G,
Spina E,
Tomson T,
Perucca E
Publication year - 1992
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1992.tb04114.x
Subject(s) - epoxide , carbamazepine , medicine , pharmacology , chemistry , epilepsy , psychiatry , biochemistry , catalysis
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.