IMPACT OF THE ADMINISTRATION METHOD AND S CHEDULE ON PASSAGE OF KETOPROFEN INTO THE BLOOD-STREAM

The pharmacokinetics of the non-steroidal antiinflammatory drugs are i nfluenced by circadian rhythms and ketoprofen (K) absorption by food, to investigate the influence of these two factors, 12 subjects were tr eated, in random order, orally by a fast release tablet (FR 100mg), by a fast-slow release tablet (FSR 150mg) and by an intramuscular soluti on (IM 100mg). The 3 treatments were administered, with a standardized meal, at 8 h a.m and 8 h p.m, and also at Ih p.m with FR. The daily d osing was 300mg by oral administration and 200 mg by IM route. Serum c oncentration profiles of K were determined by HPLC. The pharmacokineti c parameters of K were not modified by the time of intramuscular injec tion. The oral absorption of K (Tmax) was significantly delayed at Ih p.m and more even at 8h p.m. The maximal serum concentration (Cmax) wa s significantly decreased at Ih p.m (about 50%, p<0.001) and also at s h p.m. The oral bioavailability, evaluated by the area under the K ser um concentration curve, was not modified, those of FSR was significant ly lower than FR (6 %, p<0.05). This study shows that the time of K ad ministration delayed the Tmax and food decreased the Cmax without loss of bioavailability.