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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Circadian Changes in the Pharmacokinetics of Oral Ketoprofen
Clinical Pharmacokinetics, Volume 12, No. 5, Year 1987
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Description
Several investigations which have taken treatment time into account have shown that the pharmacokinetic parameters, the therapeutic efficacy and even the toxicity of a large number of products may vary according to the administration schedule. The present study was carried out in order to evaluate any circadian changes in pharmacokinetic parameters of ketoprofen, a new non-steroidal anti-inflammatory drug (NSAID). This randomised crossover study consisted of a single oral dose of ketoprofen 100mg administered to 8 healthy male volunteers, mean age 27.2 years, at 07.00 hours, 13.00 hours, 19.00 hours or 01.00 hours in 4 study periods during the first 3 months of the year. The order of administration was randomised, with each subject acting as his own control. A total of 14 blood and 4 urine samples were taken over a 12-hour period. The peak plasma concentration was twice as high after drug administration at 07.00 hours (13.4 ± 1 mg/L) than after other administration times (13.00 hours: 6.9 ± 1; 19.00 hours: 7.2 ± 0.7; 01.00 hours: 6.3 ± 0.5 mg/L) [p < 0.001]. The time to reach peak concentration was much longer after drug administration at 01.00 hours (135 ± 16.7 min) than at 07.00 (73.1 ± 14.1 min), 13.00 (75 ± 16.5 min) or 19.00 hours (82.5 ± 12.7 min) [p < 0.05]. The lag time was significantly longer at 01.00 hours than at 13.00 hours (p < 0.01). The absorption rate constant after treatment at 01.00 hours was less than at the other times of administration (p < 0.05). The bodyweight-corrected area under the curve (AUC0–12) was greater after 07.00 hours than after 13.00 (p < 0.01) or 19.00 hours (p < 0.05) and greater after 01.00 hours than after 13.00 hours (p < 0.05). The elimination half-life was significantly longer after administration at 01.00 hours than after 19.00 hours (p < 0.05), while the total clearance was lowest at 07.00 hours. Cosinor analysis demonstrated statistically significant circadian rhythms for all pharmacokinetic parameters described above. The amount of ketoprofen eliminated in the urine was delayed, and was significantly greater after the administration at 01.00 hours than 07.00 hours or 19.00 hours (p < 0.01). The relationship between absorption, diffusion and/or elimination mechanisms of the drug are discussed. © 1987, ADIS Press Limited. All rights reserved.
Authors & Co-Authors
Ollagnier, Michel
France, Saint-etienne
Hôpital Bellevue Chu de Saint-étienne
France, Paris
Cnrs Centre National de la Recherche Scientifique
Décousus, Hervè A.
France, Saint-etienne
Hôpital Bellevue Chu de Saint-étienne
France, Paris
Cnrs Centre National de la Recherche Scientifique
Cherrah, Yahya
France, Saint-etienne
Hôpital Bellevue Chu de Saint-étienne
France, Paris
Cnrs Centre National de la Recherche Scientifique
Lev́i, Fraņcis Albert
France, Saint-etienne
Hôpital Bellevue Chu de Saint-étienne
France, Paris
Cnrs Centre National de la Recherche Scientifique
Mechkouri, Mohamed
France, Saint-etienne
Hôpital Bellevue Chu de Saint-étienne
France, Paris
Cnrs Centre National de la Recherche Scientifique
Reinberg, Alain E.
France, Saint-etienne
Hôpital Bellevue Chu de Saint-étienne
France, Paris
Cnrs Centre National de la Recherche Scientifique
Statistics
Citations: 55
Authors: 6
Affiliations: 2
Identifiers
Doi:
10.2165/00003088-198712050-00003
ISSN:
03125963
Research Areas
Health System And Policy
Participants Gender
Male