The pharmacokinetics of oxcarbazepine and its active metabolite 10-hydroxy-carbazepine in healthy subjects and in epileptic patients treated with phenobarbitone or valproic acid.
The kinetics of oxcarbazepine (OXC) and its active metabolite 10-hydroxy-carbazepine (10-OH-CZ) after a single oral OXC dose (600 mg) were compared in healthy control subjects and in epileptic patients treated with phenobarbitone or sodium valproate (n = 8 in each group). In all groups, serum 10-OH-CZ concentrations were much higher than those of the parent drug. In patients on valproate, the kinetics of OXC and 10-OH-CZ did not differ significantly from those observed in controls. In patients on phenobarbitone, AUC values of both OXC and 10-OH-CZ were lower than in controls (2.9 +/- 0.4 vs 5.1 +/- 0.7 microg ml(-1) h and 89 +/- 7 vs 119 +/- 10 microg ml(-1) h respectively, means +/- s.e. mean, P < 0.05), whereas 10-OH-CZ half-lives were only marginally shorter (17 +/- 1 h vs 20 +/- 2 h, NS). These data indicate that the biotransformation of OXC and 10-OH-CZ may be accelerated by concomitant treatment with phenobarbitone but that the magnitude of this effect is unlikely to be of great clinical significance.
Tartara
A
A
Institute of Neurology C. Mondino, Pavia, Italy.
Galimberti
C A
CA
Manni
R
R
Morini
R
R
Limido
G
G
Gatti
G
G
Bartoli
A
A
Strada
G
G
Perucca
E
E
D000284:Administration, Oral; D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D000078330:Oxcarbazepine; D010634:Phenobarbital / Q000627:therapeutic use; D014635:Valproic Acid / Q000627:therapeutic use
C039775:10,11-dihydro-10-hydroxycarbamazepine; D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid; D000078330:Oxcarbazepine; D010634:Phenobarbital