The influence of food on the disposition of the antiepileptic oxcarbazepine and its major metabolites in healthy volunteers.
The effect of food on the pharmacokinetics of the antiepileptic oxcarbazepine (OXC) was investigated in healthy volunteers. Six healthy male volunteers were treated with single peroral doses of 600 mg of oxcarbazepine (Trileptal) after overnight fasting or a fat- and protein-rich breakfast. Mean (+/- SD) areas under the plasma concentration-time curves (AUC) of the major component in plasma, the active monohydroxy metabolite (MHD), which is responsible for the therapeutic effect in man, were 672 (25) mumol L-1 h when given to the fasted volunteers and 780 (31) mumol L-1 h (p = 0.042) when given after a substantial breakfast. Mean (+/- SD) maximum concentrations (Cmax) were 25.5 (4.8) mumol L-1 when given to the fasted volunteers and 31.4 (5.3) mumol L-1 (p = 0.025) when given after breakfast. Thus, the average AUC was increased by 16% and Cmax by 23% when oxcarbazepine was given with food. The times at which Cmax was reached (tmax) as well as the terminal half-lives were not influenced by concomitant intake of food. The tolerability was the same whether oxcarbazepine was given before or after food in healthy volunteers. The slight effect of food on the kinetics of oxcarbazepine should be of little therapeutic consequence.
Degen
P H
PH
Ciba-Geigy Limited, Pharmaceuticals Division, Basel, Switzerland.
Flesch
G
G
Cardot
J M
JM
Czendlik
C
C
Dieterle
W
W
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004435:Eating / Q000502:physiology*; D005215:Fasting / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078330:Oxcarbazepine
D000927:Anticonvulsants; D002220:Carbamazepine; D000078330:Oxcarbazepine