Chronopharmacology: Circadian Rhythm-Based Optimization of Drug Therapy- A Comprehensive Review

ABSTRACT Chronopharmacology is the branch of pharmacology that studies how the timing of drug administration, relative to endogenous circadian rhythms, influences drug pharmacokinetics, pharmacodynamics, efficacy, and toxicity. Nearly every physiological process hormone secretion, enzyme activity, gastric pH, hepatic blood flow, receptor density, and cell-cycle progression oscillates over a period of approximately twenty-four hours under the control of a hierarchical network of molecular clocks anchored in the suprachiasmatic nucleus. Because these rhythms modulate the absorption, distribution, metabolism, and excretion of drugs as well as the sensitivity of their molecular targets, the same dose of a drug can produce markedly different therapeutic and adverse effects depending on the clock hour at which it is administered. This review synthesises current understanding of the molecular architecture of the mammalian circadian clock and traces its influence on chronopharmacokinetics and chronopharmacodynamics. Clinical evidence is examined across four therapeutic areas in which dosing-time effects are best documented systemic hypertension, oncology (chronomodulated chemotherapy and immunotherapy), nocturnal asthma, and psychiatric/neurological disorders — together with an overview of pulsatile and chronomodulated drug-delivery technologies engineered to align drug release with disease chronopathology. The persistent controversy surrounding bedtime antihypertensive dosing is discussed to illustrate the methodological challenges that continue to face the field. As wearable biosensors, digital chronotyping, and pharmacometric modelling mature, chronopharmacology is positioned to become an integral, evidence-based component of individualised drug therapy.