[Impact of the method and timing of administration on the systemic transport of ketoprofen].
The pharmacokinetics of the non-steroidal antiinflammatory drugs are influenced by circadian rhythms and ketoprofen (K) absorption by food, to investigate the influence of these two factors, 12 subjects were treated, in random order, orally by a fast release tablet (FR 100 mg), by a fast-slow release tablet (FSR 150 mg) and by an intramuscular solution (i.m. 100 mg). The 3 treatments were administered, with a standardized meal, at 8 h a.m and 8 h p.m, and also at 1 h p.m with FR. The daily dosing was 300 mg by oral administration and 200 mg by i.m. route. Serum concentration profiles of K were determined by HPLC. The pharmacokinetic parameters of K were not modified by the time of intramuscular injection. The oral absorption of K (Tmax) was significantly delayed at 1 h p.m and more even at 8 h p.m. The maximal serum concentration (Cmax) was significantly decreased at 1 h p.m (about 50%, p < 0.001) and also at 8 h p.m. The oral bioavailability, evaluated by the area under the K serum concentration curve, was not modified, those of FSR was significantly lower than FR (6%, p < 0.05). This study shows that the time of K administration delayed the Tmax and food decreased the Cmax without loss of bioavailability.
Laboratoire de Toxicologie et de Pharmacocinétique, Hôpital Ambroise Paré, Boulogne-Billancourt, France.
B
B
Delhotal Landes
N
N
Decout
P
P
Molinier
B
B
Flouvat
D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002940:Circadian Rhythm; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004435:Eating; D005504:Food Analysis; D006801:Humans; D007273:Injections, Intramuscular; D007660:Ketoprofen / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D011897:Random Allocation; D013607:Tablets
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D013607:Tablets; D007660:Ketoprofen
Répercussion du mode et du rythme d'administration sur le passage systémique du kétoprofène.