Cutaneous absorption of indomethacin from two topical preparations in volunteers.

Abstract

The percutaneous absorption of indomethacin in 0.5 % or 1 % solution or 1 % gel at a dose of 50 mg or 100 mg indomethacin was compared in a randomized complete block design in seven healthy volunteers. The formulations were applied over an area of 12 dm(2) under an 8 h occlusion dressing. In addition, in the same volunteers the plasma concentration curves were determined after a single oral dose of 50 mg indomethacin. Indomethacin and some of its metabolites were determined with modified, existing assays using HPLC-fluorescence or gas chromatography-mass spectrometry. On the basis of a newly developed method, it was possible to separate and quantify O-desmethylindomethacin and N-deschlorobenzoyl-O-desmethylin-domethacin. After cutaneous administration of the two drug formulations, peak indomethacin plasma concentration of 95 ng/ml and 130 ng/ml were found between 4 and 8 h; the cutaneous bioavailability was approximately 20 % of the oral dose, as judged by comparing the areas under the plasma concentration time curves (AUC) and the amount of metabolites excreted into the urine. Percutaneous absorption did not change the metabolic pattern in the urine that is obtained after oral administration.