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Theoretical and computational basis for drug bioavailability determinations using pharmacological data. II. Drug input ⇄ response relationships

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Abstract

Mathematical expressions and approaches to the computation of rates and extents of drug bioavailability for implementation on analog and digital computers are derived. The equivalency of expressions derived on the basis of assuming compartment models to an approach based on using experimentally determined weighting functions is demonstrated. The relative merits of the two techniques are discussed: their application for use with temporal pharmacological data is emphasized. The applicability of the computational techniques to determining the availability of drugs at local sites of action (biophasic availability) and to computing preabsorptive drug release into the gastrointestinal contents (gastrointestinal bioavailability) is pointed out. An approach to computationally predicting in vivo blood level or pharmacological response vs. time profiles from in vitro dissolution testing results is presented and its limitations are discussed.

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Authors and Affiliations

  1. Interdisciplinary Drug Engineering and Assessment Laboratory (IDEAL), Department of Industrial and Physical Pharmacy, School of Pharmacy and Pharmacal Sciences, Purdue University, 47907, West Lafayette, Indiana

    Victor F. Smolen

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  1. Victor F. Smolen
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Research supported by Food and Drug Administration Contract No. 73-23, Alcon Laboratories, and the Purdue Biomedical Engineering Center.

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Smolen, V.F. Theoretical and computational basis for drug bioavailability determinations using pharmacological data. II. Drug input ⇄ response relationships. Journal of Pharmacokinetics and Biopharmaceutics 4, 355–375 (1976). https://doi.org/10.1007/BF01063124

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