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 absorptionlag times on day 5. The maximum concentration and the area under the curve over one 24-h dosage period (AUG0_24) were significantly higher with the LCFD, both on day 1 and on day 5. For AUC0_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 (Ae), but the difference was only significant on day 1 (14 %). The elimination rate constant (K~) 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 4 h after intake of the medication. This resulted in a greater extent of ketoprofen absorption with the LCFD than