Effect of valpromide on the pharmacokinetics of carbamazepine-10, 11-epoxide.
The single oral dose pharmacokinetics of carbamazepine-10, 11-epoxide (CBZ-E) were investigated in six normal volunteers during a control session and during concurrent treatment with valpromide (VPM) (300 mg twice daily for 8 days). VPM caused a prolongation of the CBZ-E half-life from 6.4 +/- 1.4 to 20.5 +/- 6.3 h and decreased CBZ-E clearance from 73.5 +/- 20.0 to 23.5 +/- 4.0 ml h-1 kg-1 (P less than 0.01). These results suggest that the elevation of plasma CBZ-E levels in patients receiving carbamazepine and VPM in combination is due to inhibition of epoxide hydrolase in the liver.
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D014635:Valproic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*
D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid; C012227:carbamazepine epoxide; C004651:dipropylacetamide