Effect of phenobarbital on the pharmacokinetics of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine.
The single oral dose kinetics of carbamazepine-10,11-epoxide (CBZ-E), the active metabolite of carbamazepine, were studied in six epileptic patients, stabilized on phenobarbital (PB) monotherapy, and in six drug-free health volunteers. The epoxide metabolite was administered as an enteric-coated tablet at the dose of 200 mg to the patients and at the dose of 100 mg to the volunteers. Patients had a significantly higher plasma clearance of CBZ-E than the control group (mean values +/- SD = 220.2 +/- 63.5 versus 112.5 +/- 46.0 ml/h/kg, p less than 0.007) and a significantly shorter plasma half-life (mean values +/- SD = 4.3 +/- 1.0 versus 6.7 +/- 0.8 h, p less than 0.0015). These results suggest that PB induces CBZ-E metabolism.
Spina
E
E
Psychiatric Hospital, Institute of Pharmacology, Messina, Italy.
Martines
C
C
Fazio
A
A
Trio
R
R
Pisani
F
F
Tomson
T
T
D000328:Adult; D001682:Biological Availability; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004347:Drug Interactions; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D010634:Phenobarbital / Q000494:pharmacology* / Q000627:therapeutic use
D002220:Carbamazepine; C012227:carbamazepine epoxide; D010634:Phenobarbital