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Life sciences · Journal article
Theoretical and Natural Science · September 22, 2026
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Chronopharmacology examines how biological time shapes drug disposition, target sensitivity, and therapeutic outcomes. Chronotherapeutic strategies have entered clinical practice in hypertension, rheumatoid arthritis, asthma, and cancer. Existing reviews, however, largely catalogue clinical evidence without systematically integrating how the circadian regulatory network, from core molecular oscillators to peripheral tissue outputs, affects pharmacokinetics and pharmacodynamics. This review summarizes the multi-level circadian mechanisms in mammals and uses this framework to examine the circadian basis of drug pharmacokinetics and pharmacodynamics. We systematically searched PubMed and Web of Science for chronopharmacology literature published between 1972 and 2025. The mammalian circadian system is organized around CLOCK /BMAL1-PER/CRY transcription-translation feedback loops, with the suprachiasmatic nucleus (SCN) integrating light and feeding signals and coordinating peripheral clocks through autonomic, endocrine, and behavioral pathways. Circadian regulation of hepatic drug metabolism, the morning peak in myocardial infarction, and clock-dependent immune responses illustrate how biological time shapes drug response. At the same time, the conflicting MAPEC/Hygia and TIME trial findings in hypertension chronotherapy indicate that universal dosing-time rules are limited. We conclude that dosing time should be evaluated as a drug- and patient-specific precision medicine variable rather than a one-size-fits-all rule.