CHRONOPHARMACOKINETICS OF ETHANOL .1. REVIEW OF LITERATURE AND THEORETICAL CONSIDERATIONS

  • 1 January 1976
    • journal article
    • review article
    • Vol. 3  (3) , 237-262
Abstract
Pharmacokinetic parameters are generally assumed to be invariate with the time of day, although circadian variation of drug metabolism and drug response is known. To investigate chronovariation in the disappearance rate of a substance from the blood, the drug ethanol is considered because its disappearance approximates a linear course until very low blood levels are attained. Theoretical considerations are presented for chronovariation of elimination constants for hypothetical drugs following exponential and zero-order models. The substitution of a sinusoidal function for the rate-constants in pharmacokinetic differential equations is proposed and graphed. Rhythmicity within elimination curves can apparently only be determined by repetition of the experiment at different times of the diel period. The expectation that a rate-constant estimated at 1 time of the day may be valid for another part of the day carries with it an unknown risk. No pharmacokinetic analysis can be considered definitive unless chronopharmacokinetic variation of parameters is considered.

This publication has 15 references indexed in Scilit: