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Comparative physiological pharmacokinetics of fentanyl and alfentanil in rats and humans based on parametric single-tissue models

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An Erratum to this article was published on 01 August 1995

Abstract

The objectives of this investigation were to characterize the disposition of fentanyl and alfentanil in 14 tissues in the rat, and to create physiological pharmacokinetic models for these opioids that would be scalable to man. We first created a parametric submodel for the disposition of either drug in each tissue and then assembled these submodels into whole-body models. The disposition of fentanyl and alfentanil in the heart and brain and of fentanyl in the lungs could be described by perfusion-limited 1-compartment models. The disposition of both opioids in all other examined tissues was characterized by 2- or 3-compartment models. From these models, the extraction ratios of the opioids in the various tissues could be calculated, confirming the generally lower extraction of alfentanil as compared to fentanyl. Assembly of the single-tissue models resulted in a whole-body model for fentanyl that accurately described its disposition in the rat. A similar assembly of the tissue models for alfentanil revealed non-first-order elimination kinetics that were not apparent in the blood concentration data. Michaelis-Menten parameters for the hepatic metabolism of alfentanil were determined by iterative optimization of the entire model. The parametric models were finally scaled to describe the disposition of fentanyl and alfentanil in humans.

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Authors and Affiliations

  1. Hospital Pharmacy, Malmö General Hospital, S-214 01, Malmö, Sweden

    Sven Björkman

  2. Department of Anesthesia, Stanford University School of Medicine, 94305, Stanford, California

    Sven Björkman, D. Russell Wada & Donald R. Stanski

  3. Department of Pharmaceutics, School of Pharmacy, State University of New York, 14260, Buffalo, New York

    William F. Ebling

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  1. Sven Björkman
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  2. D. Russell Wada
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  3. Donald R. Stanski
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  4. William F. Ebling
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Additional information

Supported in part by the National Institute on Aging, RO1-AG-4594, and the Anesthesia/Pharmacology Research Foundation.

An erratum to this article is available at http://dx.doi.org/10.1007/BF02353643.

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Björkman, S., Wada, D.R., Stanski, D.R. et al. Comparative physiological pharmacokinetics of fentanyl and alfentanil in rats and humans based on parametric single-tissue models. Journal of Pharmacokinetics and Biopharmaceutics 22, 381–410 (1994). https://doi.org/10.1007/BF02353862

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