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An extended physiological pharmacokinetic model of methadone disposition in the rat: Validation and sensitivity analysis

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Abstract

An extended physiological model of methadone disposition in the rat was constructed and evaluated in various tests of model validity. A separate circulation model of the fetus was included due to the large tissue concentration differences obtained after a constant rate infusion but also to propose the use of this type of model for optimization of toxicological tests. Simulations were performed with the animal model and scaled-up models of humans to elucidate the determinants of methadone dispostion. The rationale of the use of an extended model for methadone was also discussed.

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Authors and Affiliations

  1. Department of Pharmacokinetics and Biopharmaceutics, BMC, Uppsala University, Box 580, S-751 23, Uppsala, Sweden

    Johan L. Gabrielsson

  2. Unit of Biomedical Systems Analysis, Uppsala University, Box 2103, S-750 02, Uppsala, Sweden

    Torgny Groth

Authors
  1. Johan L. Gabrielsson
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  2. Torgny Groth
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Additional information

This work was supported by the Svenssons Foundation for Medical Research, the Royal Hvitfeld Establishment, and C. D. Carlssons Foundation.

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Gabrielsson, J.L., Groth, T. An extended physiological pharmacokinetic model of methadone disposition in the rat: Validation and sensitivity analysis. Journal of Pharmacokinetics and Biopharmaceutics 16, 183–201 (1988). https://doi.org/10.1007/BF01062260

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  • DOI: https://doi.org/10.1007/BF01062260

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