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Circadian Changes of Drug Disposition in Man

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Summary

Circadian (≈24 hours) and other endogenous biological rhythms, detectable at all levels of organisation, constitute a temporal structure in all animal species, including man. Circadian, circannual, and other rhythmic changes in biological susceptibility and response of organisms to a large variety of physical and chemical agents, including medications and foods, are rather common phenomena. A better understanding of periodic and thus predictable changes in drug effects can be attained through consideration of three complementary concepts, the chronopharmacokinetics of a drug (rhythmic changes in its pharmacokinetics), the chronesthesy (rhythmic changes in susceptibility of target biosystems to the drug), and the chronergy (the drug-integrated overall effects).

The chronopharmacokinetics of many drugs have been evaluated in man including sodium salicylate, aspirin, indomethacin, paracetamol (acetaminophen), phenacetin, amidopyrine, theophylline, digitalis, Propranolol, clorazepate, hexobarbitone (hexobarbital), lithium, phenytoin (diphenylhydantoin), nortriptyline, ethanol, erythromycin, ampicillin, sulfasymazine, sulphanilamide, cisplatin (cis-diammine dichloroplatinum), d-xylose, ferrous sulphate, potassium chloride, hydrocortisone and prednisolone, among others. The roles presumably played by circadian rhythms in drug metabolising liver enzymes and kidney function are summarised, and the practical implications of chronopharmacokinetics, aiming both to improve in a quantitative manner the metabolic fate of a drug and its effectiveness, are discussed.

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Authors and Affiliations

  1. E.R. de Chronobiologie Humaine, CNRS No. 5 and Fondation A. de Rothschild, Paris, France

    A. Reinberg & M. H. Smolensky

  2. Health Science Center at Houston, University of Texas School of Public Health, Houston, USA

    A. Reinberg & M. H. Smolensky

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  1. A. Reinberg
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Reinberg, A., Smolensky, M.H. Circadian Changes of Drug Disposition in Man. Clin Pharmacokinet 7, 401–420 (1982). https://doi.org/10.2165/00003088-198207050-00002

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