title: Effect of vigabatrin and gabapentin on phenytoin pharmacokinetics in the dog.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. matark@ksu.edu.sa
authors.forename: K M
authors.initials: KM
authors.lastname: Matar
authors.forename: P J
authors.initials: PJ
authors.lastname: Nicholls
authors.forename: S A
authors.initials: SA
authors.lastname: Bawazir
authors.forename: M I
authors.initials: MI
authors.lastname: Al-Hassan
authors.forename: A
authors.initials: A
authors.lastname: Tekle
mesh_terms: 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
chemical_list: D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D000077206:Gabapentin; D020888:Vigabatrin