Circadian clock-controlled drug metabolism and transport

Abstract

1. Metabolism and transport of many drugs oscillate with times of the day (solar time), resulting in circadian time-dependent drug exposure and pharmacokinetics.

2. Time-dependent pharmacokinetics (also known as chronopharmacokinetics) is associated with time-varying drug effects and toxicity.

3. 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.

4. 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.

Keywords:

• Circadian clock
• drug metabolism
• drug transport
• molecular mechanisms
• chronopharmacokinetics

Disclosure statement

The authors have declared that no conflict of interest exists.

Additional information

Funding

This work was supported by the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (No. 2017BT01Y036), the Natural Science Foundation of Guangdong Province (No. 2017A03031387) and the Guangzhou Science and Technology Project (No. 201904010472).