Pharmacokinetic profile of flunarizine after single and multiple dosing in epileptic patients receiving comedication.
This preliminary clinical study describes the pharmacokinetic characteristics of flunarizine (FLN) following single and multiple dosing in epileptic patients receiving comedication. Three groups [phenytoin (PHT) only, carbamazepine (CBZ) only, and PHT plus CBZ] of four patients each were studied. Large interindividual differences, but no statistically significant differences in pharmacokinetic parameters, were observed between the three groups. Following a single dose, mean values (and ranges) for apparent clearance, volume distribution, and elimination half-life (t1/2) were 0.504 L/h/kg (0.086-1.119), 12,431 L (1,959-20,920), and 308 h (61-506), respectively. FLN had no effect on PHT or CBZ steady-state levels but PHT or CBZ appeared to induce the metabolic disposition of FLN. The effect of dose on FLN kinetics could not be evaluated in this preliminary study.
Kapetanovic
I M
IM
Epilepsy Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland 20892.
Torchin
C D
CD
Kupferberg
H J
HJ
Treiman
D M
DM
Di Giorgio
C
C
Barber
K
K
Norton
L
L
Lau
M
M
Whitley
L
L
Cereghino
J J
JJ
D000328:Adult; D002220:Carbamazepine / Q000008:administration & dosage / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005444:Flunarizine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage / Q000493:pharmacokinetics
D002220:Carbamazepine; D010672:Phenytoin; D005444:Flunarizine