EFFECT OF DIET ON THE SINGLE-DOSE AND MULTIPLE-DOSE PHARMACOKINETICS OF SUSTAINED-RELEASE KETOPROFEN

The indirect effect of diet on the single-and multiple-dose pharmacoki netics of sustained-release ketoprofen was studied in 16 healthy male volunteers. In an open, cross-over design, 200 mg ketoprofen was admin istered as a gastric-juice-resistant, sustained-release tablet once da ily during two periods of 5 days. A low-calorie/low-fat diet (LCFD) wa s given in the first period and a high-calorie/high-fat diet (HCFD) in the second period. The first meal on each day was given 4 h after dru g intake. Ketoprofen plasma concentrations were measured over 24 h aft er the first dose on day 1 and over 36 h after the final dose on day 5 of each period. On average, plasma concentrations of ketoprofen were higher with the LCFD than with the HCFD. With the HCFD there was a ten dency to longer absorption-lag times on day 5. The maximum concentrati on and the area under the curve over one 24-h dosage period (AUC(0-24) ) were significantly higher with the LCFD, both on day 1 and on day 5. For AUC(0-24) the differences were on average 15 % (day 1) and 24 % ( day 5). The same tendency was observed for the amount excreted in urin e over 24 h (A(e)), but the difference was only significant on day 1 ( 14 %). The elimination rate constant (K-beta) and the mean residence t ime were similar for the two diets, both on day 1 and on day 5. From t hese results, we conclude that there was an acute indirect effect of d iet when a meal was had 4h after intake of the medication. This result ed in a greater extent of ketoprofen absorption with the LCFD than wit h the HCFD. The absorption rate was apparently not influenced by this acute effect. The longer gastric residence time of ketoprofen with the HCFD may be the result of a long-term indirect effect on gastric empt ying rate. If the extreme difference between the diets in this study i s taken into account, it seems unlikely that the observed indirect eff ects have implications for clinical practice.