The 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 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 over 24 hr. after administration of the PT dose. PT administration was continued with oral supplementary dose of VGB (60 mg/kg) for another week and then plasma samples were collected for analysis of PT levels. The same protocol 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 parameters 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 (t1/2), (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 marked reduction in systemic clearance of the latter in the dog.
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Matar, K.M., Nicholls, P.J., Tekle, A. et al. Effect of vigabatrin and gabapentin on phynytoin pharmacokinetics in the dog. Eur. J. Drug Metab. Pharacokinet. 25, 189–193 (2000). https://doi.org/10.1007/BF03192312