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KMID : 0043319940170050364
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Archives of Pharmacal Research
1994 Volume.17 No. 5 p.364 ~ p.370
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Prediction of drug-Drug Interaction During Oral Absorption of Carrier-Mediated Compounds in Humans
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Oh Doo-Man
Gordon L. Amidon
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Abstract
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A microscopic mass balance approach has been developed to estimate the extent and rate of absorption for camier-mediated comounds. For the case competitive inhibition in the presence of an inhibitor which shares the same camier, the fraction dose absorbed (F) and absorption rate constant () 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 simultaion of the absorption of some aminopenicilins. Predicted fractions dose absorbed and absorption rate constants of ampicilin and amoxicilin were significantly reduced in the presence of a 6-times higher molar dose of cyclacilin. The drug-drug interactions on the competitive absroption of camier-mediated compounds were determined with regard to F and . Predicted decreases in F for some aminopenicilins corrlated well with decrease in the urinary recovery in humans reported in the literature. Predicted decrease in the mean absorption rate constant () explain the delays in the time of peak plasma concentration () reported in humans.
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KEYWORD
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Abosorption, Absorption rate constnat, Aminopenicillin, Bioavailability, Permeability
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