Application of microdialysis for the determination of muscle and subcutaneous tissue concentrations after oral and topical ibuprofen administration

Background: The topical administration of non-steroidal antiinflammatory dr ugs (NSAIDs) is widely used for the treatment of soft tissue pain. However, it is not known whether effective tissue concentrations are reached with t he topical route. Objective: To evaluate and compare unbound muscle and subcutaneous tissue i buprofen concentrations with use of microdialysis after topical and oral ad ministration. Methods: In a 2-way crossover design, 11 healthy volunteers received either 800 mg oral ibuprofen or 16 g of 5% ibuprofen gel applied onto the skin of the thigh (defined area, 17 x 19 cm). Microdialysis catheters were inserte d into the medial vastus muscle (25 to 30 mm) and into the subcutaneous adi pose layer of the thigh (4 to 5 mm), Dialysate was collected in 20-minute i ntervals up to 5 hours. Results: Essentially all of the orally administered dose was recovered in u rine as ibuprofen or metabolites during 24 hours, but only about 0.55% of t he topically administered dose was recovered. The relative systemic bioavai lability of ibuprofen gel, based on urine recovery data, was (mean +/- SD) 0.57% +/- 0.30%. Mean values of the dialysate areas under the drug concentr ation-time curves after topical and oral administration were 731.2 +/- 605. 0 and 176.6 +/- 122.9 ng.h.mL(-1) for subcutaneous tissue and 63.5 +/- 90.3 and 213.4 +/- 117.2 ng.h.mL(-1) for muscle, respectively. Muscle dialysate concentrations after topical administration varied considerably among the subjects. Conclusion: These results suggest that, if target tissue concentrations cor relate directly with the degree of pain relief, patients with pain caused b y dermal or subcutaneous tissue damage will have greater pain relief after topical administration of ibuprofen accompanied with less systemic side eff ects. In addition, a proportion of patients with muscle pain may also exper ience pain relief from topical ibuprofen.