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 pharmacokinetics of sustained-release ketoprofen was studied in 16 healthy male volunteers. In an open, cross-over design, 200 mg ketoprofen was administered as a gastric-juice-resistant, sustained-release tablet once daily during two periods of 5 days. A low-calorie/low-fat diet (LCFD) was 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 drug intake. Ketoprofen plasma concentrations were measured over 24 h after 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 tendency to longer absorption-lag times on day 5. The maximum concentration 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 urine 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 time were similar for the two diets, both on day 1 and on day 5. From these results, we conclude that there was an acute indirect effect of diet when a meal was had 4h after intake of the medication. This resulted in a greater extent of ketoprofen absorption with the LCFD than with 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 emptying rate. If the extreme difference between the diets in this study is taken into account, it seems unlikely that the observed indirect effects have implications for clinical practice.