The effect of oral lipids and circulating lipoproteins on the metabolism of drugs.
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.
Patel
Jigar P
JP
University of Alberta, Dentistry/Pharmacy Centre, Edmonton, Canada.
Brocks
Dion R
DR
D000818:Animals; D001682:Biological Availability; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology; D018565:Food-Drug Interactions; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008055:Lipids / Q000494:pharmacology*; D008074:Lipoproteins / Q000502:physiology*; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D004041:Dietary Fats; D005227:Fatty Acids; D007527:Isoenzymes; D008055:Lipids; D008074:Lipoproteins; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System