Skip Navigation LinksHome > May 1990 - Volume 72 - Issue 5 > Comparative Tissue Concentration Profiles of Fentanyl and Al...
Anesthesiology:
Laboratory Investigations: PDF Only

Comparative Tissue Concentration Profiles of Fentanyl and Alfentanil in Humans Predicted from Tissue/Blood Partition Data Obtained in Rats.

Björkman, Sven Ph.D.; Stanski, Donald R. M.D.; Verotta, Davide; Harashima, Hideyoshi Ph.D.

Collapse Box

Abstract

The steady-state tissue/blood partition coefficients of fentanyl and alfentanil were determined in 13 organs and tissues in the rat. A 6-h infusion of both drugs was used in order to achieve steady-state. Blood and tissue concentrations of drugs were measured by gasliquid chromatography. The partition coefficients of fentanyl were two- to 30-fold higher than those of alfentanil. These data were then used in a physiologic pharmacokinetic model describing the disposition of the two opioids in humans. The model predicted the plasma pharmacokinetics of these drugs in humans reasonably well. However, simulation beyond 24 h after a bolus administration showed a terminal half-life of 20 h for fentanyl, i.e., an elimination phase that has not yet been described in actual pharmacokinetic studies. In keeping with this, the volume of distribution of fentanyl in the model was also larger than expected. The simulated tissue concentration curves of fentanyl and alfentanil in humans could be used to explain the propensity of fentanyl to give secondary peaks in plasma concentration curves and the difference in effect kinetics between the two opioids. Physiologic pharmacokinetic modeling, based on measured data in small animals, can generate information that is not obtainable by empirical methods in humans.
(C) 1990 American Society of Anesthesiologists, Inc.
Publication of an advertisement in Anesthesiology Online does not constitute endorsement by the American Society of Anesthesiologists, Inc. or Lippincott Williams & Wilkins, Inc. of the product or service being advertised.
Login

Article Tools

Share

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.