Molecular Basis of Chronopharmaceutics

Jun 10, 2011Journal of pharmaceutical sciences

How molecular processes affect the timing of drug effects

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Abstract

Chronotherapeutics may optimize drug effectiveness and safety based on the timing of intake.

Physiological processes, including sleep-wake cycles and metabolism, exhibit biological rhythms over 24-hour periods.
Disruptions to these rhythms can lead to the emergence or worsening of various health conditions.
The mammalian circadian pacemaker, located in the suprachiasmatic nucleus, regulates these biological rhythms.
Clock genes play a role in controlling circadian rhythms, influencing physiology, pathology, and behavior.
Mutations in CLOCK genes can alter the expression of genes, affecting how drugs are metabolized and their effects.
Understanding these biological rhythms can enhance the application of pharmaceuticals by addressing individual variability.

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Many pathophysiological circumstances vary during 24 h periods. Many physiologic processes undergo biological rhythms, including the sleep-wake rhythm and metabolism. Disruptive effect in the 24 h variations can manifest as the emergence or exacerbation of pathological conditions. So, chronotherapeutics is gaining increasing interest in experimental biology, medicine, pharmacy, and drug delivery. This science and the plethora of information should be used intelligently for optimizing the effectiveness and safety of the drug, relying on the timing of drug intake. These chronopharmacological findings are affected by not only the pharmacodynamics but also pharmacokinetics of drugs. The mammalian circadian pacemaker is located in the suprachiasmatic nucleus. The molecular mechanisms are associated with Clock genes that control the circadian rhythms in physiology, pathology, and behavior. Clock controls several diseases such as metabolic syndrome, cancer, and so on. CLOCK mutation influences the expression of both rhythmic and nonrhythmic genes in wild-type tissues. These genotypic changes lead to phenotypic changes, affecting the drug pharmacokinetic and pharmacodynamic parameters. This review is intended to elaborate system regulating biological rhythms and the applicability in pharmaceutics from viewpoints of the intraindividual and interindividual variabilities of Clock genes.

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Molecular Basis of Chronopharmaceutics

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