Single-dose kinetics of an enteric-coated formulation of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine.
The kinetics of an enteric-coated formulation of carbamazepine-10,11-epoxide (CBZ-E) were studied in healthy subjects. A single oral dose of 100 mg of CBZ-E was given to eight subjects. Four of them were also given a single oral dose of 200 mg of CBZ-E. Plasma concentrations of CBZ-E and urinary excretion of the end metabolite trans-10,11-dihydroxy-10,11-dihydro-carbamazepine (trans-CBZ-diol) were determined by high performance liquid chromatography. Plasma kinetics of CBZ-E fitted an open one-compartment model with plasma elimination half-life of 7.4 +/- 1.8 h (mean +/- SD). The clearance was 105 +/- 17 ml/kg/h and the apparent volume of distribution 1.1 +/- 0.2 L/kg assuming complete bioavailability. There was no indication of dose-dependent elimination of CBZ-E. The recovery of trans-CBZ-diol in urine collected for 3 days was 67 +/- 9% of the given dose. This enteric-coated formulation may thus in the future be used for the evaluation of the clinical effects of CBZ-E in patients.
Spina
E
E
Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden.
Tomson
T
T
Svensson
J O
JO
Faigle
J W
JW
Bertilsson
L
L
D000328:Adult; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D013608:Tablets, Enteric-Coated
D013608:Tablets, Enteric-Coated; D002220:Carbamazepine; C012227:carbamazepine epoxide