Relative bioavailability of ketoprofen 20% in a poloxamer-lecithin organogel

Purpose. The bioavailability of a single, topically applied, 200-mg dose of ketoprofen (delivered in a ketoprofen 20% gel) relative to a single 50-mg oral dose in healthy volunteers was studied. Methods. This was an open-label crossover study. The subjects were randomized to receive an oral 50-mg ketoprofen capsule or a single topical dose of ketoprofen 20% in a poloxamer-lecithin organogel (PLO). Treatment was followed by a one-week washout period. Blood samples were collected at intervals up to 10 hours after administration, and plasma ketoprofen concentrations were determined by high-performance liquid chromatography with ultraviolet or mass spectrometry detection. Noncompartmental pharmacokinetic values were obtained after each dose, and relative bioavailability was calculated. Results. Eight healthy volunteers were enrolled in and completed the study. Topical absorption of ketoprofen was highly variable among the subjects over the 10-hour sampling period. The median oral maximum plasma concentration (C-max) exceeded the topical C-max by nearly 200-fold (4.15 versus 0.021 mug/mL) (p = 0.001). The median relative bioavailability of topical ketoprofen was 0.48%, with individual subjects' values ranging from 0.18% to 2.1 %. Conclusion. The relative bioavailability of ketoprofen was low and highly variable when the drug was administered as a single dose in a PLO-based ketoprofen 20% gel.