Plasma and Cutaneous Drug Levels after Topical Application of Piroxicam Gel: A Study in Healthy Volunteers

Abstract

Two studies in healthy male and female volunteers (aged 18–65 years) were undertaken to determine plasma and cutaneous levels of drug following topical application of piroxicam gel. Twelve subjects applied piroxicam gel to the knee (1 g of 0.5% Feldene gel) at baseline and then after 6, 12 and 24 h. Plasma was collected after 1,2,4,6,14,24,28 and 48 h and piroxicam content determined by high-pressure liquid chromatogrÄphy (HPLC). For the majority of samples collected, piroxicam levels were below the limit of detection (LOD) of the assay and the maximum recorded plasma level in any subject at any time point was 75.4 ng/ml. A single application of gel was administered to the forearms of four groups each of 6 subjects, and biopsy samples of the stratum corneum (skin surface biopsy, SBB) and epidermis/dermis were taken after 0.5, 1, 2 and 4 h. The levels of piroxicam were again measured in each sample by HPLC. The highest levels of piroxicam were found in the superficial skin surface biopsy with the lowest levels recorded in the skin surface biopsies nearest the viable epidermis. The mean tissue concentrations ranged from 160 to 640 ng per sample (calculated to be 80–320 µg/g of tissue). The mean levels of piroxicam in a 4-mm punch biopsy showed an increase with time after application, rising from 60.3 to 94.6 ng per biopsy (calculated to be 2.4 to 3.8 µg/g of tissue). It may be concluded that piroxicam rapidly permeates through the stratum corneum into the epidermis/dermis after application of the gel. Low and often undetectable plasma levels of drug were observed after topical application of piroxicam gel in a manner comparable to clinical usage.