PHARMACOKINETICS AND BIOAVAILABILITY OF PERCUTANEOUS IBUPROFEN

The absorption, pharmacokinetics and bioavailability of ibuprofen (GAS 15687-27-1) were investigated for an ibuprofen gel preparation (ibuge l(R)) for percutaneous application, and compared to a standard oral ib uprofen tablet preparation. The monocentric, randomised 2-way cross-ov er study with 7-day, wash-out period was performed an 18 healthy, fema le volunteers with an average age of 26.3 +/- 4.8 years (range: 20-38 years), average weight 60.4 +/- 7.6 kg, and average height 164.7 +/- 5 .9 cm. Blood samples were taken from the volunteers before administrat ion of the tablet or gel, and periodically during 24 h after administr ation. The ibuprofen content in these samples was determined using a v alidated HPLC method. Main pharmacokinetic parameters derived from ind ividual plasma concentration-time courses included: C-max, t(max), AUC (0-->24), AUC(0-->infinity), MRT(0-->infinity), t(1/2) and F-rel. For percutaneous application of 500 mg ibuprofen (10 g 5% gel on the back, area of 20 x 20 cm) with occlusion for 2 h, a C-max of 7.1 +/- 4.4 mu g/ml (95% confidence interval (CI): 5.0-9.1) was obtained at 2.4 +/- 0.8 h (95% CI: 2.0-2.8). For oral administration of 400 mg, C-max was 36.7 +/- 7.5 mu g/ml (95% CI: 33.2-40.1) at 1.1 +/- 0.8 h (95% CI: 0.7 +/- 1.5). The (dose-corrected) relative bioavailability of the topica l ibuprofen was found to be 22 +/- 12% (95% CI: 14-30%) of that after oral administration. The plasma elimination half-life was 2.5 +/- 1.4 h (95% CI: 1.9-3.2) for topical administration and 1.8 +/- 0.5 h (95% CI: 1.6-2.1) after oral administration (not significant, p > 0.05).