Inhibition of epoxide hydrolase by valproic acid in epileptic patients receiving carbamazepine.
The effect of valproic acid (VPA) on the disposition of carbamazepine-10,11-epoxide (epoxide) was studied in five epileptic patients on chronic carbamazepine (CBZ) therapy. The individual pharmacokinetic parameters influencing epoxide disposition were determined in the presence and absence of VPA. VPA significantly decreased the clearance of unbound epoxide (an in vivo index of epoxide hydrolase activity), but did not appear to affect epoxide formation. VPA also increased the free concentrations of both CBZ and epoxide.
Robbins
D K
DK
College of Pharmacy, University of Kentucky, Lexington.
Wedlund
P J
PJ
Kuhn
R
R
Baumann
R J
RJ
Levy
R H
RH
Chang
S L
SL
D000293:Adolescent; D001798:Blood Proteins / Q000378:metabolism; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D004827:Epilepsy / Q000188:drug therapy / Q000201:enzymology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008297:Male; D011485:Protein Binding; D014635:Valproic Acid / Q000009:adverse effects*
D001798:Blood Proteins; D002220:Carbamazepine; D014635:Valproic Acid; D004851:Epoxide Hydrolases; C012227:carbamazepine epoxide