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 drugs (NSAIDs) is widely used for the treatment of soft tissue pain. However, it is not known whether effective tissue concentrations are reached with the topical route. Objective To evaluate and compare unbound muscle and subcutaneous tissue ibuprofen concentrations with use of microdialysis after topical and oral administration. 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 × 19 cm). Microdialysis catheters were inserted into the medial vastus muscle (25 to 30 mm) and into the subcutaneous adipose layer of the thigh (4 to 5 mm). Dialysate was collected in 20‐minute intervals up to 5 hours. Results Essentially all of the orally administered dose was recovered in urine as ibuprofen or metabolites during 24 hours, but only about 0.55% of the topically administered dose was recovered. The relative systemic bioavailability of ibuprofen gel, based on urine recovery data, was (mean ± SD) 0.57% ± 0.30%. Mean values of the dialysate areas under the drug concentration–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 correlate directly with the degree of pain relief, patients with pain caused by dermal or subcutaneous tissue damage will have greater pain relief after topical administration of ibuprofen accompanied with less systemic side effects. In addition, a proportion of patients with muscle pain may also experience pain relief from topical ibuprofen. Clinical Pharmacology & Therapeutics (1999) 65, 357–368; doi: