Influence of single and repeated doses of oxcarbazepine on the pharmacokinetic profile of felodipine.
Eight healthy male volunteers (age 25-41 years) entered an open-label, within-subject study. They were treated for 13 consecutive days with felodipine (FEL) extended-release tablets, 10 mg daily. On day 6, oxcarbazepine (OXC) 600 mg was given in the morning, and from day 7 to 13, the daily dose was increased to 450 mg b.i.d. Blood samples for measurement of FEL and its pyridine metabolite (determined by gas-chromatography) were drawn just before dosing and at 2, 4, 6, 8, 10, 12, and 24 h after dosing on days 5, 6, and 13. Steady-state pharmacokinetic parameters of FEL and its pyridine metabolite were not influenced by the single dose of OXC. Repeated coadministration of OXC significantly reduced the area under the concentration-time curve (AUC0-24) of FEL by 28% and the FEL maximum plasma concentration (Cmax) by 34%. This reduction in FEL bioavailability is much smaller than that observed after co-administration of carbamazepine (CBZ) (i.e., 94%).
Zaccara
G
G
Department of Neurological and Psychiatric Sciences, University of Florence, Italy.
Gangemi
P F
PF
Bendoni
L
L
Menge
G P
GP
Schwabe
S
S
Monza
G C
GC
D000284:Administration, Oral; D000328:Adult; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004334:Drug Administration Schedule; D004347:Drug Interactions; D015736:Felodipine / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D000078330:Oxcarbazepine; D011725:Pyridines / Q000493:pharmacokinetics
D011725:Pyridines; D002220:Carbamazepine; D015736:Felodipine; D000078330:Oxcarbazepine