Circadian clock-controlled drug metabolism and transport

Abstract

Metabolism and transport of many drugs oscillate with times of the day (solar time), resulting in circadian time-dependent drug exposure and pharmacokinetics.Time-dependent pharmacokinetics (also known as chronopharmacokinetics) is associated with time-varying drug effects and toxicity.This review summarizes drug-metabolizing enzymes and transporters with rhythmic expressions in the liver, intestine and/or kidney. Correlations of these diurnal proteins with circadian variations in drug exposure and effects/toxicity are covered. We also discuss the molecular mechanisms for circadian control of enzymes and transporters.Mechanism-based chronopharmacokinetics would facilitate a better understanding of chronopharmacology and the design of time-specific drug delivery systems, ultimately leading to improved drug efficacy and minimized toxicity.