Effect of vigabatrin and gabapentin on phynytoin pharmacokinetics in the dog

The study was aimed at investigating whether or not the kinetics of intrave nously administered phenytoin (PT) was altered by oral administration of vi gabatrin (VGB) or gabapentin (GBP). A group of five beagle dogs were given a daily dose of PT (12 mg/kg, i.v.) for a period of 1 week. On day 8, plasma samples were serially collected ov er 24 hr, after administration of the PT dose. PT administration was contin ued with oral supplementary dose of VGB (60 mg/kg) for another week and the n plasma samples were collected for analysis of PT levels. The same protoco l was followed for the PT (12 mg/kg, IV) - GBP (300 mg caps., PO) study on a separate group (n=5) of dogs. Orally administered GBP did not significantly alter the pharmacokinetic par ameters of parentral PT. VGB, however markedly changed the drug's kinetics as evidenced by a 31% (P=0.015) reduction in total body clearance (CL) and increase of over 45% in half-life (t(1/2)), (P=0.013) and area under the pl asma 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 marked reduction in systemic clea rance of the latter in the dog.