Summary
A one-compartment model with first-order absorption has provided good fits to five sets of indomethacin data and four sets of ketoprofen data taken at different times of day. There was substantial variation in the model parameters with time of administration and most of the features of this variation applied equally to both drugs. From the data examined, the source of variation appears to be mainly in the absorption phase and this was confirmed using a chronokinetic analysis, in which simultaneous fits were obtained with time-variant rate parameters. However, there may also be circadian variation in protein binding.
The danger of quoting parameter values for either of these two drugs based on administration at a single time of day has been illustrated, and this may well be true for other drugs.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Reinberg A, Smolensky MH (1982) Circadian changes of drug disposition in man. Clin Pharmacokinet 7: 401–420
Godfrey KR (1988) The effects of circadian rhythms on pharmacokinetic quantities. Biomed Meas Infor Contr 2: 14–24
Godfrey KR (1989) Chronopharmacology and its application to the development of theophylline treatment schedules for asthma. Eur J Clin Pharmacol 36: 103–109
Clench J, Reinberg A, Dziewanowska Z, Ghata J, Smolensky MH (1981) Circadian changes in the bioavailability and effects of indomethacin in healthy subjects. Eur J Clin Pharmacol 20: 359–369
Ollagnier M, Decousus H, Cherrah Y, Levi F, Mechkouri M, Queneau P, Reinberg A (1987) Circadian changes in the pharmacokinetics of oral ketoprofen. Clin Pharmacokinet 12: 367–378
Curtis AR, Sweetenham WP (1987) Facsimile/Chekmat Users' Manual. AERE Harwell Report No. 12805
Vener KJ, Moore JG (1987) Chronobiologic properties of the alimentary canal affecting xenobiotic absorption. Ann Rev Chronopharmacol 4: 257–281
Decousus H, Ollagnier M, Cherrah Y, Perpoint B, Hocquart J, Queneau P (1986) Chronokinetics of ketoprofen infused intravenously at a constant rate. Ann Rev Chronopharmacol 3: 321–322
Cuisinaud G, Guissou P, Sassard J (1984) Chronopharmacokinetic study of indomethacin. Ann Rev Chronopharmacol 1: 341–344
Guissou P, Cuisinaud G, Llorca G, Leleune E, Sassard J (1983) Chronokinetic study of a prolonged release form of indomethacin. Eur J Clin Pharmacol 24: 667–670
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Aronson, J.K., Chappell, M.J., Godfrey, K.R. et al. Modelling circadian variation in the pharmacokinetics of non-steroidal anti-inflammatory drugs. Eur J Clin Pharmacol 45, 357–361 (1993). https://doi.org/10.1007/BF00265955
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00265955