European Journal of Clinical Pharmacology

, Volume 20, Issue 5, pp 359–369 | Cite as

Circadian changes in the bioavailability and effects of indomethacin in healthy subjects

  • J. Clench
  • A. Reinberg
  • Z. Dziewanowska
  • J. Ghata
  • M. Smolensky
Originals

Summary

Nine subjects, 19 to 29 years old (2 females) synchronized with activity from 07.00 to 00.00 received a single daily oral dose (100 mg) of indomethacin at fixed hours: 07.00, 11.00, 15.00, 19.00 and 23.00, in random order and at weekly intervals. 1) Chronopharmacokinetics: Venous blood (sampled at: 0, 0.33, 0.67, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0 and 10.0 h post ingestion) was used for plasma drug determination. Circadian changes in peak height, time to peak, area under the concentration-time curve and the disappearance rate were used to characterize indomethacin chronopharmacokinetics. A circadian rhythm of both peak height and time to peak was validated. An evening ingestion led to smallest peak height and longest time to peak. 2) Circadian changes in a set of effects: Eleven physiologic variables were investigated (post absorption) at Δt=2 h. Circadian rhythms were detected: i) on control day and ii) with evening ingestion for ten of the eleven variables indicating that the subjects' temporal structure did not become altered by an evening ingestion, whereas it did become so by morning ones. Transient changes (n minutes post absorption) measured as T240 min post absorption/Tcontrol day, same clock hour ratio were also circadian rhythmic for most variables. Again, evening ingestion appeared least disturbing.

Key words

chronopharmacology indomethacin pharmacokinetics iatrogensis chronotherapeutics 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Carosella L, Di Nardo P, Bernabei R, Cocchi A, Carbonin P (1979) Chronopharmacokinetics of digitalis. Circadian variations of betamethyl-digotoxin serum levels after oral administration. In: Reinberg A, Halberg F (eds) Chronopharmacology, Pergamon Press, Oxford New York, pp 125–133Google Scholar
  2. Del Ponte A, Capani F, Sensi S (1979) Circadian variation of digotoxin effects in healthy subjects. In: Reinberg A, Halberg F (eds) Chronopharmacology Pergamon Press, Oxford New York, pp 135Google Scholar
  3. DiSanto A, Chodos D, Halberg F (1975) Chronobioavailability of three erythromycin test preparations assessed by each of 4 indices: time to peak, peak, nadir and area. Chronobiologia 2 (Suppl. 1) p 17Google Scholar
  4. Döring GK, Riecke H (1952) Über tagesperiodische Schwankungen der Kapillarresistenz. Klin Wochenschr 30: 1098Google Scholar
  5. 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
  6. Halberg F, Tong YL, Johnson EA: Circadian system phase: an aspect of temporal morphology. Precedure and illustrative examples. In: Mayersbach H von (ed) The cellular aspects of biorhythms. Springer, Berlin Heidelberg New York, pp 20–48Google Scholar
  7. Halberg F, Johnson EA, Nelson W, Runge W, Southern R (1972) Autorhythmometry procedures for physiologic self-measurements and their analysis. Physiol Teacher 1: 1–11Google Scholar
  8. Halberg F, Carandente F, Cornelissen GL, Katinas GS (1977) Glossary of chronobiology. Chronobiologia 4 (Suppl. 1): 153–154Google Scholar
  9. Hucker HB, Zacchei AG, Cox SV, Brodie DA, Cantwell NHR (1966) Studies on the absorption, distribution and excretion of indomethacin in various species. J Pharmacol Exp Therap 153: 237–249Google Scholar
  10. Huskisson EC (1976) Chronopharmacology of anti-rheumatic drugs with special reference to indomethacin. In: Huskisson EC, Velo GP (eds) Inflammatory arthropathies. Excerpta Medica, Amsterdam, pp 99–105Google Scholar
  11. Katz AM, Pearson CM, Kennedy JM (1965) A clinical trial of indomethacin in rheumatoid arthritis. Clin Pharmacol Ther 6: 25–30Google Scholar
  12. Kwan KC, Breault GO, Umbenhauer ER, McMahon EG, Duggan DE (1976) Kinetics of indomethacin absorption, elimination and enterohepatic circulation in man. J Pharmacokinet Biopharm 4: 255–280Google Scholar
  13. Kyle GM, Smolensky MH, Thorne LG, Hsi B, Robinson A, McGovern JP (1981) Circadian rhythm in the pharmacokinetics of orally administered theophylline. In: Smolensky MH, McGovern JP, Reinberg A (eds) Recent advances of chronobiology in allergy and immunology. Pergamon Press, OxfordGoogle Scholar
  14. Labrecque G, Doré F, Laperriere A, Pérusse F, Bélanger PM (1979) Chronopharmacology II. Variations in the carrageenin-induced edema in the action and the plasma levels of indomethacin. In: Reinberg A, Halberg F (eds) Chronopharmacology. Pergamon Press, Oxford, pp 231–238Google Scholar
  15. Maxey Kyle G, Smolensky MH, McGovern JP (1979) Circadian variation in the susceptibility of rodents to the toxic effects of theophylline. In: Reinberg A, Halberg F (eds) Chronopharmacology. Pergamon Press, Oxford, pp 239–244Google Scholar
  16. McGovern JP, Smolensky MH, Reinberg A (1977) Circadian and circamensual rhythmicity in cutaneous reactivity to histamine and allergenic extract. In: Smolensky M, Reinberg A (eds) Chronobiology in allergy and immunology. CC Thomas, Springfield, IL, pp 79–116Google Scholar
  17. Minors DS, Waterhouse JM (1979) Chronopharmacokinetics of ethanol in human subjects. In: Reinberg A, Halberg F (eds) Chronopharmacology, Pergamon Press, Oxford, pp. 323Google Scholar
  18. Pearson CM (1966) Letter to the editor. Clin Pharmacol Ther 7: 116Google Scholar
  19. Reinberg A (1976) Advances in human chronopharmacology. Chronobiologia 3: 151–166Google Scholar
  20. Reinberg A, Halberg F (1971) Circadian chronopharmacology. Annu Rev Pharmacol 11: 455–492Google Scholar
  21. Reinberg A, Reinberg MA (1977) Circadian changes of the duration of action of local anaesthetic agents. Arch Pharmacol 297: 149–152Google Scholar
  22. Reinberg A, Sidi E, Ghata J (1965) Circadian reactivity rhythms of human skin to histamine or allergen and the adrenal cycle. J Allergy 36: 273–283Google Scholar
  23. Reinberg A, Zagula-Mally Z, Ghata J, Halberg F (1967) Circadian rhythms in durations of salicylate excretion referred to phase of excretory rhythms and routine. Proc Soc Exp Biol (NY) 124: 826–832Google Scholar
  24. Reinberg A, Halberg F, Falliers C (1974a) Circadian timing of methylprednisalone effects in asthmatic boys. Chronobiologia 1: 333–347Google Scholar
  25. Reinberg A, Clench J, Aymard N, Gaillot M, Bourdon R, Gervais P, Abulker C, Dupont J (1974b) Rythmes circadiens des paramétres de l'éthanolémie provoquée chez six hommes adultes jeunes et sains. CR Acad Sci Paris 278: 1503–1505Google Scholar
  26. Reinberg A, Clench J, Aymard N, Gaillot M, Bourdon R, Gervais P, Abulker C, Dupont J (1975a) Variations circadiennes des effets de l'éthanol et de l'éthanolemie chez l'homme adulte sain (étude chronopharmacologique) J Physiol (Paris) 70: 1–22Google Scholar
  27. Reinberg A, Clench J, Ghata J, Halberg F, Abulker C, Dupont J, Zagula-Mally Z (1975b) Rythmes circadiens des paramétres de l'excrétion urinaire du salicylate (chronopharmacocinétique) chez l'homme adulte sain. CR Acad Sci Paris 280: 1697–1699Google Scholar
  28. Reinberg A, Levi F, Guillet PM, Burke JT, Nicolai A (1978) Chronopharmacological study of antihistamines in man with special reference to terfenadine. Eur J Clin Pharmacol 14: 245–252Google Scholar
  29. Schoeller R, Busigny M, Jayle MF (1957) Méthode de dosage des 17–21 déhydroxy-20-cétostéroides. Sem Hop Paris (Arch Biol Med) 33: 2–12Google Scholar
  30. Sturtevant FM, Sturtevant RP, Scheving LE, Pauly JE (1975) Chronopharmacokinetics of ethanol in man. Chronobiologia 2 (Suppl 1) pp 69Google Scholar
  31. Swoyer J, Lakatua DJ, Haus E, Warner T, Sackett L (1975) Circadian rhythm in ethanol disappearance rate from human plasma. Chronobiologia 2 (Suppl. 1) pp 71Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • J. Clench
    • 1
    • 2
  • A. Reinberg
    • 1
  • Z. Dziewanowska
    • 3
  • J. Ghata
    • 1
  • M. Smolensky
    • 2
  1. 1.Equipe de Recherche de Chronobiologie Humaine, CNRS no 105Fondation A. de RothschildParisFrance
  2. 2.School of Public HealthThe University of Texas Health Science Center at HoustonHoustonUSA
  3. 3.Department of Medical Research Hoffmann LaRoche Pharmaceutical Inc.NutleyUSA

Personalised recommendations