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Circadian regulation of transporter expression and implications for drug disposition
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SYSNO ASEP 0542597 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Circadian regulation of transporter expression and implications for drug disposition Author(s) Pácha, Jiří (FGU-C) RID, ORCID
Balounová, Kateřina (FGU-C) RID, ORCID
Soták, M. (SE)Source Title Expert Opinion on Drug Metabolism & Toxicology. - : Taylor & Francis - ISSN 1742-5255
Roč. 17, č. 4 (2021), s. 425-439Number of pages 15 s. Language eng - English Country GB - United Kingdom Keywords drug transport ; drug elimination ; circadian rhythms ; solute carriers ; ATP-binding cassette transporters ; liver ; intestine ; kidney Subject RIV ED - Physiology OECD category Physiology (including cytology) R&D Projects GA18-02993S GA ČR - Czech Science Foundation (CSF) Method of publishing Limited access Institutional support FGU-C - RVO:67985823 UT WOS 000604653900001 EID SCOPUS 85098689413 DOI 10.1080/17425255.2021.1868438 Annotation Introduction: Solute Carrier (SLC) and ATP-binding cassette (ABC) transporters expressed in the intestine, liver, and kidney determine the absorption, distribution, and excretion of drugs. In addition, most molecular and cellular processes show circadian rhythmicity controlled by circadian clocks that leads to diurnal variations in the pharmacokinetics and pharmacodynamics of many drugs and affects their therapeutic efficacy and toxicity.Area covered: This review provides an overview of the current knowledge on the circadian rhythmicity of drug transporters and the molecular mechanisms of their circadian control. Evidence for coupling drug transporters to circadian oscillators and the plausible candidates conveying circadian clock signals to target drug transporters, particularly transcription factors operating as the output of clock genes, is discussed.Expert opinion: The circadian machinery has been demonstrated to interact with the uptake and efflux of various drug transporters. The evidence supports the concept that diurnal changes that affect drug transporters may influence the pharmacokinetics of the drugs. However, more systematic studies are required to better define the timing of pharmacologically important drug transporter regulation and determine tissue- and sex-dependent differences. Finally, the transfer of knowledge based on the results and conclusions obtained primarily from animal models will require careful validation before it is applied to humans. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2022 Electronic address https://doi.org/10.1080/17425255.2021.1868438
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