Effect of vigabatrin and gabapentin on phenytoin pharmacokinetics in the dog.
This study was aimed at investigating whether or not the kinetics of intravenously administered phenytoin (PT) was altered by oral administration of vigabatrin (VGB) or gabapentin (GBP). A daily dose of PT (12 mgkg(-1)i.v.) was given to a group of five beagle dogs for a period of 1 week. On day eight, plasma samples were serially collected over 24 h, after administration of the PT dose. PT administration was continued, along with supplementary oral VGB (60 mgkg(-1)) for another week and then plasma samples were collected for analysis of PT levels. The same protocol was followed for the PT (12 mgkg(-1), i.v.)-GBP (300 mg caps., p.o.) study on a separate group (n= 5) of dogs. Orally administered GBP did not significantly alter the pharmacokinetic parameters of parenteral PT. However VGB markedly changed the drug's kinetics, as evidenced by a 31% (P= 0.015) reduction in total body clearance (CL) and an increase of over 45% in half-life (t(1/2)), (P= 0.013) and area under the plasma PT concentration-time curve (AUC), (P= 0.044). GBP does not appear to have any pharmacokinetic interaction with PT, while coadministration of VGB and PT results in a marked reduction in systemic clearance of the latter in the dog.
Matar
K M
KM
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. matark@ksu.edu.sa
Nicholls
P J
PJ
Bawazir
S A
SA
Al-Hassan
M I
MI
Tekle
A
A
D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D003509:Cyclohexanecarboxylic Acids; D004285:Dogs; D004347:Drug Interactions; D000077206:Gabapentin; D008297:Male; D010672:Phenytoin / Q000493:pharmacokinetics*; D020888:Vigabatrin / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D000077206:Gabapentin; D020888:Vigabatrin