Phenytoin auto-induction.
Information regarding phenytoin auto-induction is sparse and conflicting. However, confirmation of the presence or absence of auto-induction by phenytoin could have important implications in phenytoin therapy and research. This was an open, randomized, three-way crossover study in which each of the eighteen volunteers received three different formulations of phenytoin, which was allocated in a random order. The period effect between each crossover was determined to assess the effect of the previous exposure to phenytoin on the area under the concentration-time curve (AUC). The point estimate ratio of AUC(o-t) for the third dose relative to the first dose was 81.19% with 90% t-confidence limits of 74.37% to 88.00% and p = 0.3847. The point estimate ratio of AUC(o-infinity) for the third dose relative to the first dose was 76.25% with 90% t-confidence limits of 65.3% to 87.2% and p = 0.7169. These results suggest that the AUC (o-infinity) and AUC(o-t) measured after the third dose of phenytoin was statistically significantly smaller than those measured after the first dose. This decrease in AUC after the third dose of phenytoin is probably caused by enhanced elimination of the drug as a result of enzyme induction.
Chetty
M
M
Department of Experimental and Clinical Pharmacology, University of Witwatersrand, Johannesburg, South Africa.
Miller
R
R
Seymour
M A
MA
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004790:Enzyme Induction; D006801:Humans; D008297:Male; D010672:Phenytoin / Q000097:blood / Q000493:pharmacokinetics*; D012016:Reference Values; D013810:Therapeutic Equivalency
D000927:Anticonvulsants; D010672:Phenytoin