Modelling circadian variation in the pharmacokinetics of non-steroidal anti-inflammatory drugs.
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.
Aronson
J K
JK
University Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford, UK.
Chappell
M J
MJ
Godfrey
K R
KR
Yew
M K
MK
D000328:Adult; D002940:Circadian Rhythm; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007660:Ketoprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological
D007660:Ketoprofen; D007213:Indomethacin