Percutaneous Absorption, Metabolic Profiling, and Excretion of the Penetration Enhancer Azone after multiple dosing of an Azone-Containing Triamcinolone Acetonide Cream in Humans

Abstract

Radioactive Azone (1.6%; 1-dodecylazacycloheptan-2-one) was incorporated in a therapeutic formulation containing triamcinolone acetonide at a concentration of 0.05%. This cream (TAZ) was applied for four consecutive days to human volunteers on the same 24-cm2 application area on the forearm for 12h under occlusion. The percutaneous absorption of Azone as measured in the excreta appeared to be only 3.47 ± 0.33% during the whole study period. Azone-derived radioactivity was predominantly excreted by the kidneys (97.8 ± 0.4%). From the urinary excretion plot, it could be deduced that the flux of Azone through human skin increased during the study period, reaching a plateau within 2–3 d. Accumulation of Azone in the stratum corneum did not occur. Only unchanged Azone could be detected in the stratum corneum. Excretion was mainly in the form of very polar metabolites. Compared with pure Azone, the therapeutic formulation did not influence the metabolism, excretion route, or urinary elimination rate of the penetration enhancer.