Chronopharmacokinetic Aspects with Special Reference to Cardiovascular Drugs

  • B. Bruguerolle
Conference paper


Some drugs have a narrow therapeutic range, and it has been shown for these drugs that therapeutic monitoring is necessary since there is a close relationship between the pharmacological effect and the blood level. This constitutes the basis for pharmacokinetic studies involving the study of the fate of drugs in the organism related to time, i.e., absorption, distribution, metabolism, and elimination processes. Mathematical models are used to simplify and summarize these processes and thus simulate concentrations of the drug in all parts of the organism. This concept underlies the search for a constant blood level of the drug thought to be necessary to obtain an effect as constant as possible. Obviously, the chronopharmacological data deny this concept, since the efficacy, toxicity and kinetics of drugs have been reported to depend on the moment of its administration (Reinberg and Halberg 1971), (Reinberg and Ghata 1990). Chronopharmacokinetics concerns the study of the temporal changes in absorption, distribution, metabolism, and elimination of a drug and thus the influence of time of administration on mathematical parameters that describe these different stages. The chronokinetics of more than 100 drugs has been reported in animal or in man, as reviewed by Reinberg and Smolensky (1982), Lemmer (1981 b), Bruguerolle (1983 a, b, 1987), and Levi et al. (1989).


Hepatic Blood Flow Circadian Variation Cardiovascular Drug Constant Rate Infusion Circadian Change 
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© Springer-Verlag Berlin Heidelberg 1992

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  • B. Bruguerolle

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