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A physiologically based pharmacokinetic model for theophylline disposition in the pregnant and nonpregnant rat

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Abstract

There are numerous studies which examine the disposition of theophylline from a traditional point of view. Information about the behaviour of drugs, including theophylline, is, however, very scarce when investigating the kinetics by means of a physiological flow model. This study is concerned with the development of a predictive analytical model for the pharmacokinetics of theophylline in nonpregnant and pregnant rats. This model postulates that specific organ or tissue masses may be simulated by compartments whose elements have physiological properties, e.g., tissue volumes, blood flow, and metabolic activity. A model has been developed that has blood, brain, hepatic, muscular, pulmonary, renal, and fetal tissues. With few exceptions, the agreement was good between predicted and calculated tissue data in the pregnant and nonpregnant rats. Finally, model simulations were performed to investigate the impact of different pulmonary extraction ratios on the concentration-time profile of theophylline in a “hypothetical” human patient.

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Authors and Affiliations

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

    Johan L. Gabrielsson & Lennart K. Paalzow

  2. Department of Pharmacology, Central Research and Control Laboratory of the National Corporation of Swedish Pharmacies, S-171 03, Solna, Sweden

    Lars Nordström

Authors
  1. Johan L. Gabrielsson
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  2. Lennart K. Paalzow
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  3. Lars Nordström
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Additional information

This study was supported by grants from the Swedish Council for Planning and Coordination of Research [(FRN)82/2090].

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Gabrielsson, J.L., Paalzow, L.K. & Nordström, L. A physiologically based pharmacokinetic model for theophylline disposition in the pregnant and nonpregnant rat. Journal of Pharmacokinetics and Biopharmaceutics 12, 149–165 (1984). https://doi.org/10.1007/BF01059275

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  • DOI: https://doi.org/10.1007/BF01059275

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