Percutaneous absorption of triamcinolone acetonide from creams with and without Azone ® in humans in vivo

Abstract

A clinical study was performed in which 0.05% triamcinolone acetonide cream (TA), containing tracer amounts of 3H-labelled steroid, was applied once on the volar aspect of the right forearm for 12 h under occlusion. No Azone was incorporated in this cream. After a wash-out period, repeated dosing of TAZ, a similar cream containing 0.05% triamcinolone acetonide and 1.6% Azone, was performed on days 4–7 on the left forearm for 12 h per day under occlusion. The TAZ-cream contained tracer amounts of the 3H-labelled steroid on days 4 and 7. Absorption, distribution, and elimination of triamcinolone acetonide were followed by measuring the amounts of 3H-steroid-derived radioactivity in plasma, tape strippings, urine, and feces. Residual analysis was performed as well. During the whole study-period 6.7 ± 0.3% (mean ±S.D.) of the total applied radioactivity penetrated through the skin. The first application of TAZ resulted in a 3.2-times higher percutaneous absorption of steroid than the single application of TA, indicating an increased rate of absorption of triamcinolone acetonide in the presence of Azone. After multiple dosing of TAZ, absorption further increased to 6.8 times that of a single TA dose. Nevertheless, systemic levels of triamcinolone acetonide remained very low. Tape stripping revealed that reservoir formation of steroid was less pronounced after multiple dosing of TAZ relative to single dosing of TA, and higher levels of steroid were found in the deeper layers of the stratum corneum, immediately after removal of the last TAZ-dose. This paper reports the first evidence that Azone acts as a penetration enhancer in vivo in human skin when dosed in a therapeutic formulation.