Abstract
The effect of drug interactions with other drugs, excipients and gastrointestinal contents on their oral absorption and systemic availability have been extensively investigated over the past 50 years. These interactions can be classified as direct interactions between the drug and other drugs or components in the formulation, e.g., excipients in the gastrointestinal tract altering the drugs’ thermodynamic activity for absorption or, alternatively, the effects may be indirect through alteration of gastrointestinal transit, gastrointestinal secretions, or gastrointestinal/hepatic metabolism or elimination. Recently attention has been directed to metabolism interactions in the liver and even more recently in the gastrointestinal mucosal tissue. These interactions can be caused by direct inhibition of enzyme metabolism or enzyme induction, resulting in changes in the absorption rate and leading to altered oral bioavailability. These metabolic effects also can be indirect, through the position dependence of metabolizing enzyme levels in the gastrointestinal tract; consequently transit changes can alter metabolic profiles and systemic availability. Recent interest has been directed to carrier-mediated absorption, where drug interactions can occur through competition for carrier(s) responsible for absorption and, finally, it has been proposed that the P-glycoprotein exporter may be responsible for some of the observed drug interactions and nonlinear absorption effects. This review will focus on examples of the various types of mechanistic interactions noted above. The interaction of drugs with foods, a very important component in drug regulation today, is reviewed elsewhere in this volume. A more comprehensive survey of relevant drug-drug interaction than can be covered in this review can be found in Table 1.
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Lipka, E., Crison, J.R., Schug, B.S., Blume, H.H., Amidon, G.L. (1996). Drug Interactions in the Gastrointestinal Tract and Their Impact on Drug Absorption and Systemic Availability: A Mechanistic Review. In: D’Arcy, P.F., McElnay, J.C., Welling, P.G. (eds) Mechanisms of Drug Interactions. Handbook of Experimental Pharmacology, vol 122. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61015-8_2
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