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

Authors :
Okyar A
Ozturk Civelek D
Akyel YK
Surme S
Pala Kara Z
Kavakli IH
Source :
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.
Publication Year :
2024

Abstract

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.<br />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.<br />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.

Details

Language :
English
ISSN :
1744-7607
Volume :
20
Issue :
6
Database :
MEDLINE
Journal :
Expert opinion on drug metabolism & toxicology
Publication Type :
Academic Journal
Accession number :
38753451
Full Text :
https://doi.org/10.1080/17425255.2024.2356167