The role of the circadian timing system on drug metabolism and detoxification: an update.

Autor:	Okyar A; Department of Pharmacology, Istanbul University Faculty of Pharmacy, Istanbul, Turkiye., Ozturk Civelek D; Department of Pharmacology, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkiye., Akyel YK; Department of Medical Pharmacology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey.; Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, NC, USA., Surme S; Molecular Biology and Genetics, Koc University, Istanbul, Türkiye.; Chemical and Biological Engineering, Koc University, Istanbul, Türkiye., Pala Kara Z; Department of Pharmacology, Istanbul University Faculty of Pharmacy, Istanbul, Turkiye., Kavakli IH; Molecular Biology and Genetics, Koc University, Istanbul, Türkiye.; Chemical and Biological Engineering, Koc University, Istanbul, Türkiye.
Jazyk:	angličtina
Zdroj:	Expert opinion on drug metabolism & toxicology [Expert Opin Drug Metab Toxicol] 2024 Jun; Vol. 20 (6), pp. 503-517. Date of Electronic Publication: 2024 May 20.
DOI:	10.1080/17425255.2024.2356167
Abstrakt:	Introduction: The 24-hour variations in drug absorption, distribution, metabolism, and elimination, collectively known as pharmacokinetics, are fundamentally influenced by rhythmic physiological processes regulated by the molecular clock. Recent advances have elucidated the intricacies of the circadian timing system and the molecular interplay between biological clocks, enzymes and transporters in preclinical level. Area Covered: Circadian rhythm of the drug metabolizing enzymes and carrier efflux functions possess a major role for drug metabolism and detoxification. The efflux and metabolism function of intestines and liver seems important. The investigations revealed that the ABC and SLC transporter families, along with cytochrome p -450 systems in the intestine, liver, and kidney, play a dominant role in the circadian detoxification of drugs. Additionally, the circadian control of efflux by the blood-brain barrier is also discussed. Expert Opinion: The influence of the circadian timing system on drug pharmacokinetics significantly impacts the efficacy, adverse effects, and toxicity profiles of various drugs. Moreover, the emergence of sex-related circadian changes in the metabolism and detoxification processes has underscored the importance of considering gender-specific differences in drug tolerability and pharmacology. A better understanding of coupling between central clock and circadian metabolism/transport contributes to the development of more rational drug utilization and the implementation of chronotherapy applications.
Databáze:	MEDLINE
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