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The effect of oral lipids and circulating lipoproteins on the metabolism of drugs

& , PhD (Professor)
Pages 1385-1398 | Published online: 10 Aug 2009
 

Abstract

The oral bioavailability of many lipophilic drugs is known to increase when coadministered with fatty meals. Although such a phenomenon is typically ascribed to increased solubilization and absorption of drug, in some cases this increase in systemic exposure may be in part due to the influence of lipids on the presystemic metabolism of the affected drug. Oral lipids on their absorption may interfere with the drug metabolizing enzymes expressed in the small intestine and/or liver. Fatty acids incorporated in dietary triglyceride can modulate the expression and activity of drug metabolizing enzymes within the small intestine. Lipoproteins, which are the major carriers of lipids in the systemic circulation, can become associated with lipophilic drugs. Such a combination may influence the metabolism of lipophilic drugs through limiting their uptake into the cells thereby decreasing their metabolism. In a contrary manner, an increased uptake and metabolism of lipoprotein-bound drug may be facilitated by lipoprotein receptors mediated uptake. The components of lipoproteins may also modulate the expression or activity of hepatic and extrahepatic drug metabolizing enzymes.

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