Comparison of tissue and plasma levels of ibuprofen after oral and topical administration

Abstract

The penetration and absorption of ibuprofen (CAS 15687-27-1) from a topical gel and oral tablets were tested in an open study, performed in 17 patients with degenerative knee disorders requiring an operation. Patients administered the topical test preparation (ibugel, 3 x 375 mg ibuprofen daily) or the standard oral preparation (2 x 600 mg ibuprofen daily) for 3 days prior to the operation. Samples of blood, synovial fluid, muscle, fasciae and subcutis were obtained during the operation (15 h after the last administration) and analysed for ibuprofen content using a validated HPLC method. Different absorption profiles were observed for topical and oral administration. Oral administration led to higher concentrations in the plasma, synovial fluid and fasciae, while higher levels in the muscle and subcutis were found after topical administration. After topical application, the concentrations in the fasciae, muscle and subcutis were significantly higher than those in the blood plasma and synovial fluid (p < 0.05). Very low levels of ibuprofen were observed in the subcutis after oral administration. This can be explained by the different pathways. This study demonstrated that concentrations of ibuprofen in the various biological samples were still within therapeutically effective levels 15 h after topical or oral administration. By use of an oral comparison group, it has been possible to show that the concentrations in times directly under the site of topical application lie in the same order of magnitude as those found after preoral treatment. Therapy of intra-articular inflammatory and degenerative joint diseases requires oral administration of non-steroidal anti-inflammatory drugs (NSAIDs). However, based on the results of this study, topical therapy with NSAIDs can be recommended for soft tissue rheumatism and periarticular insertion tendinopathia.