Effect of vigabatrin and gabapentin on phenytoin pharmacokinetics in the dog

This study was aimed at investigating whether or not the kinetics of intrav enously administered phenytoin (PT) was altered by oral administration of v igabatrin (VGB) or gabapentin (GBP). A daily dose of PT (12 mg kg(-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 col lected over 24 h, after administration of the PT dose. PT administration wa s continued, along with supplementary oral VGB (60 mg kg(-1)) for another w eek and then plasma samples were collected for analysis of PT levels. The s ame protocol was followed for the PT (12 mg kg(-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 par ameters 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) a nd an increase of over 45% in half-life (t(1/2)), (P = 0.013) and area unde r 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 cl earance of the latter in the dog. (C) 2000 Academic Press.