PMID: 9523809Apr 2, 1998Paper

Application of physiologic models to predict the influence of changes in body composition and blood flows on the pharmacokinetics of fentanyl and alfentanil in patients

Anesthesiology
S BjörkmanD R Stanski

Abstract

The influence of changes in the physiologic state of a patient on the disposition of fentanyl and alfentanil is poorly understood. The aims of this study were to determine whether physiologic pharmacokinetic models for fentanyl and alfentanil, based on data from rats, could predict plasma concentrations of these opioids in humans and to determine how changes in physiology would influence the predictions of their disposition. The predictions of the models were tested against plasma concentration data from published pharmacokinetic studies. The influences of changes in body composition, cardiac output, and regional blood flows on the disposition of the opioids were simulated. The models could predict independently measured plasma concentrations of the opioids after short infusions in humans. Simulations then predicted that differences in body composition between men and women would have little influence on the pharmacokinetics of the opioids. Changes in cardiac output would affect drug redistribution, and consequently the early decay of the plasma concentrations, but not markedly influence rates of elimination. Further, the clearance of the opioids would decrease and their volumes of distribution increase with the age of the pati...Continue Reading

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