DOSE-DEPENDENCE OF THE APPARENT HALF-LIFE OF PHENYTOIN IN THE RAT

  • 1 January 1980
    • journal article
    • research article
    • Vol. 28  (1) , 3-11
Abstract
The effect of dose on phenytoin pharmacokinetics was examined in the rat. In a randomized study on 9 animals (not crossed over) it was observed that the apparent half-life (t1/2) of this drug increased 4-fold as dose was increased from 10 to 50 mg/kg (t1/2 = 64 .+-. 42 min vs. 267 .+-. 118 min, respectively; mean .+-. SD). In a crossover study on 3 animals, an even larger dose-dependent increase in t1/2 was observed (37.8 vs. 271 min). Animals [6] received the 10 and 50 mg/kg doses in a randomized crossover fashion and urine was collected for 72 h. A dose-dependent decrease in the fraction of the dose excreted as conjugates of 5-(p-hydroxyphenyl)-5-phenylhydantoin (59 .+-. 20 vs. 39 .+-. 12%) was found. Phenytoin pharmacokinetics in the rat are apparently non-linear but a simple 1-compartment Michaelis-Menten model cannot account for the observed behavior.

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