Circadian Clock-Controlled Intestinal Expression of the Multidrug -Resisttance Gene mdr1a in Mice

摘要

Daily variations in biologic functions are thought to affect the efficacy and/or toxicity of drugs; a large number of drugs cannot be expected to have the same potency at different administration times. Dosing time-dependent differences in the therapeutic effects of drugs are at least in part, due to circadian-related changes in drug disposition, for example, absorption,distribution, metabolism, and elimination. The xenobiotic transporter P-glycoprotein (P-gp), en-coded by rnultidrug resistance (mdr) genes, functions as an energy-dependent efflux pump by expelling cytotoxic substances. In mammals, P-glycoproteins are expressed in epithelial cells of several organs, including the liver, intestine, and kidney, and thus contribute to the biliary, intestinal, and renal elimination of many drugs. Because drug transporters recognize a broad range of substances, it is now well recognized that they can function as an intestinal barrier to limit oral drug absorption