MODELING CIRCADIAN VARIATION IN THE PHARMACOKINETICS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS

A one-compartment model with first-order absorption has provided, good fits to five sets of indomethacin data and four sets of ketoprofen da ta taken at different times of day. There was substantial variation in the model parameters with time of administration and most of the feat ures of this variation applied equally to both drugs. From the data ex amined, 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. Ho wever, there may also be circadian variation in protein binding.The da nger of quoting parameter values for either of these two drugs based o n administration at a single time of day has been illustrated, and thi s may well be true for other drugs.