Clinical Chronopharmacology and Chronotherapy of Asthma

  • A. Reinberg
  • P. Gervais
  • C. Gaultier
  • F. Lévi


As a result of endogenous biological rhythms both desired and undesired effects of a therapeutic agent vary as a function of the time at which it is given in the 24 h scale among other periods. Emphasis will be given here to circadian (≃24 h) chronopharmacology and chronotherapy. A better understanding of these pre-dictable changes can be reached by using several new concepts (Reinberg 1976). Chronopharmacokinetics (or chronokinetics, Reinberg 1976, Sturtevant 1976) means circadian changes of parameters and curve patterns used to characterize the pharmacokinetics of an agent. Chronesthesy (Reinberg 1976) indicates circadian changes in the susceptibility of target biosystems to an agent and involves receptors, cells, tissues, organs and organ systems. The chronergy (Reinberg 1976) of an agent designates its overall effects on the organism as a result of both its chronokinetics and the chronesthesy of target biosystems. Circadian changes in desired effects are usually namend chronoeffectiveness while time dependent changes in undesired effects are described as chronotolerance.


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  1. Bruguerolle B (1984) Chronopharmacologie. Ellipses, Edition Marketing, ParisGoogle Scholar
  2. Ceresa F, Angeli A, Boccuzzi G, Molina G (1969) Once-a-day neutrally stimulated and basal ACTH secretion phases in man and their response to corticoid inhibition. J Clin Endocrinol Metab 29: 1074–1082PubMedCrossRefGoogle Scholar
  3. Gaultier C, Reinberg A, Girard F (1977) Circadian rhythms in lung resistance and dynamic lung compliance of healthy children. Effects of two bronchodilators. Respir Physiol 31: 169–182Google Scholar
  4. Grant SD, Forsham PH, Di Raimondo VC (1965) Suppression of 17-hydroxy corticosteroids in plasma and urine after single and divided doses of triamcinolone. N Engl J Med 273: 1115–1118PubMedCrossRefGoogle Scholar
  5. Krieger DT (1979) Endocrine Rhythms. Raven Press, New YorkGoogle Scholar
  6. Law CM, Marchant JL, Honour JW, Preece MA, Warner JO (1986) Nocturnal adrenal suppression in asthmatic children taking inhaled beclomethasone dipropionate. Lancet 1: 942–944PubMedCrossRefGoogle Scholar
  7. Lemmer B (1984) Chronopharmakologie, 2nd edn. Wissenschaftliche Verlagsgesellschaft StuttgartGoogle Scholar
  8. Moeller H (1985) Chronopharmacology of hydrocortisone and 9-fluoro-hydrocortisone in the treatment of congenital adrenal hyperplasia. Eur J Pediatr 144: 370–373PubMedCrossRefGoogle Scholar
  9. Nichols T, Nugent CA, Tyler FH (1965) Diurnal variations in suppression of adrenal function by glucocorticoids. J Clin Endocrinol Metab 25: 343–349PubMedCrossRefGoogle Scholar
  10. Postma D, Koether G, Meurs H, Keyser J (1984) Slow release terbutaline in nocturnal bronchial obstruction: relation of terbutaline dosage and blood levels with circadian changes in peak flow values. Ann Rev Chronopharmacol 1:101–108Google Scholar
  11. Reinberg A (1976) Advance in human chronopharmacology. Chronobiologia 3: 151–166PubMedGoogle Scholar
  12. Reinberg A, Clench J, Ghata J, Halberg F, Abulker C, Dupont J, Zagulla-Mally Z (1975) Rythmes circadiens des parametres de l’excretion urinaire du salicylate (chronopharmacocinetique) chez l’homme adulte sain. C R Acad Sci Paris 280: 1697–1699Google Scholar
  13. Reinberg A, Gervais P, Chaussade M, Fraboulet G, Duburque B (1983) Circadian changes in effectiveness of corticosteroids in 8 patients with allergic asthma. J Allergy Clin Immunol 71: 425–433PubMedCrossRefGoogle Scholar
  14. Reinberg A, Ghata J, Halberg F, Apfelbaum M, Gervais P, Boudon P, Abulker Ch, Dupont J (1971) Distribution temporelle du traitement de l’insuffisance corticosurrenalienne. Essai de chronotherapeutique. Ann Endocrinol (Paris) 32: 566–573Google Scholar
  15. Reinberg A, Guillet P, Gervais P, Ghata J, Vignaud D, Abulker C (1977) One-month chronotherapy (Dutimelan 8–15 mite). Control of the asthmatic condition without adrenal suppression and circadian rhythm alteration. Chronobiologia 4: 295–312Google Scholar
  16. Reinberg A, Halberg F (1971) Circadian chronopharmacology. Ann Rev Pharmacol 11: 455–492PubMedCrossRefGoogle Scholar
  17. Reinberg A, Pauchet F, Ruff F, Gervais A, Smolensky M, Levi F, Gervais P, Chaouat D, Abella ML (1986) Once-a-day (morning versus evening) sustained release theophylline in nocturnal asthma. Ann Rev Chronopharmacol 3: 147–150Google Scholar
  18. Reinberg A, Smolensky M (1982) Circadian changes of drug disposition in man. Clin Pharmacokinet 7: 401–420PubMedCrossRefGoogle Scholar
  19. Reinberg A, Smolensky M (1983) Biological Rhythms and Medicine. Springer, New York HeidelbergGoogle Scholar
  20. Reinberg A, Smolensky M, Levi F (1981) Clinical chronopharmacology. Biomedicine 34: 171–178PubMedGoogle Scholar
  21. Smolensky M, Reinberg A, Queng J (1981) The chronobiology and chronopharmacology of allergy. Ann Allergy 47: 234–252PubMedGoogle Scholar
  22. Smolensky M, Scott PH, Barnes PJ, Jonckman J (1986) The chronopharmacology and chronotherapy of asthma. Ann Rev Chronopharmacol 2: 229–273Google Scholar
  23. Sturtevant FM (1976) Chronopharmacokinetics of ethanol 1. Review of the literature and theoretical considerations. Chronobiologia 3: 237–262PubMedGoogle Scholar

Copyright information

© Springer-Verlag, Berlin Heidelberg New York 1987

Authors and Affiliations

  • A. Reinberg
  • P. Gervais
  • C. Gaultier
  • F. Lévi

There are no affiliations available

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