Inhibition of human liver microsomal epoxide hydrolase by valproate and valpromide: in vitro/in vivo correlation

摘要: On the basis of drug interactions with carbamazepine epoxide, it has been hypothesized that valproic acid and valpromide are inhibitors epoxide hydrolase, but role hydrolase in these not clearly established. In this study, therapeutic concentrations (less than 1 mmol/L) 10 mumol/L) inhibited hydrolysis styrene oxide human liver microsomes preparations purified microsomal hydrolase. Valpromide (KI = 5 was 100 times more potent 550 as an inhibitor microsomes. After administration to volunteers, transdihydrodiol formation clearance decreased 20% by (blood concentration approximately 113 67% less mumol/L). For both valpromide, a striking similarity exists between vitro vivo inhibitory potencies. Valproic first drugs known inhibit important detoxification enzyme, at concentrations.