Oxcarbazepine: preliminary clinical and pharmacokinetic studies on a new anticonvulsant.
Oxcarbazepine is a new anticonvulsant, currently undergoing clinical trials. Its spectrum of antiepileptic action, and its chemical structure, resemble those of carbamazepine, though the 2 drugs have no pharmacologically active metabolites in common. In a study of 7 adults with poorly controlled partial epilepsy, progressive substitution of oxcarbazepine for carbamazepine left seizure control unaltered in 4 and improved in 3, whilst 5 became more alert and one was rendered ataxic. Three subjects became hyponatraemic. There were no other adverse effects. Plasma levels of the drug and its pharmacologically active 10-hydroxy derivative were measured sequentially over 4 days after a single drug dose at the outset of therapy in 5 subjects. Calculated pharmacokinetic parameter values for the drug, assuming complete oral bioavailability, were: absorption lag time 2.07 +/- 1.61 h: absorption rate constant 8.328 +/- 8.941 h-1: apparent volume of distribution 3.937 +/- 2.222 L kg-1: oral clearance 2.898 +/- 1.439 L kg-1: elimination rate constant 0.609 +/- 0.261 h-1 (half-life 1.26 +/- 0.37 h), while the metabolite had a formation rate constant of 0.593 +/- 0.233 h-1, and an elimination rate constant of 0.082 +/- 0.014 h-1 (half-life 8.74 +/- 1.79 h). Even with a single dose, peak plasma metabolite levels were substantially higher than those of the parent drug. Oxcarbazepine appears to be a promising alternative to carbamazepine as an anticonvulsant, although in view of its rapid elimination it probably serves mainly as a prodrug for its 10-hydroxy metabolite.
Hooper
W D
WD
Department of Medicine, University of Queensland, Brisbane.
Dickinson
R G
RG
Dunstan
P R
PR
Pendlebury
S C
SC
Eadie
M J
MJ
D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D000078330:Oxcarbazepine
D000927:Anticonvulsants; D002220:Carbamazepine; D000078330:Oxcarbazepine