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Prediction of drug-drug interaction during oral absorption of carrier-mediated compounds in humans

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Abstract

A microscopic mass balance approach has been developed to estimate the extent and rate of absorption for carrier-mediated compounds. For the case of the competitive inhibition in the presence of an inhibitor which shares the same carrier, the fraction dose absorbed (F) and absorption rate constant (ka) of a drug can be calculated from its concentration profile in the intestinal lumen. Absorption parameters obtained by single-pass perfusion experiments were used in the simulation of the absorption of some aminopenicillins. Predicted fractions dose absorbed and absorption rate constants of ampicillin and amoxicillin were significantly reduced in the presence of a 6-times higher molar dose of cyclacillin. The drug-drug interactions on the competitive absorption of carrier-mediated compounds were determined with regard to F and ka. Predicted decreases in F for some aminopenicillins correlated well with decreases in the urinary recovery in humans reported in the literature. Predicted decreases in the mean absorption rate constant\((\bar k_a )\) explain the delays in the time of peak plasma concentration (Tmax) reported in humans.

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Authors and Affiliations

  1. College of Pharmacy, Hyosung Women's University, Hayang, 713-702, Kyungbuk, Korea

    Doo-Man Oh

  2. College of Pharmacy, The University of Michigan, 48109-1065, Ann Arbor, Michigan, U.S.A.

    Gordon L. Amidon

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  1. Doo-Man Oh
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  2. Gordon L. Amidon
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Oh, DM., Amidon, G.L. Prediction of drug-drug interaction during oral absorption of carrier-mediated compounds in humans. Arch. Pharm. Res. 17, 364–370 (1994). https://doi.org/10.1007/BF02974178

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  • DOI: https://doi.org/10.1007/BF02974178

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