Percutaneous absorption of amorolfine following a single topical application of an amorolfine cream formulation

In an open-label, parallel-group, randomized study percutaneous absorption of 14C-labelled amorolfine incorporated into a cream formulation was assessed in healthy male volunteers (n = 12). A single dose of 0.5 g of the 0.25% cream formulation was applied to 100 cm2 of intact (n = 6) and stripped (n = 6) skin for 24 h using occlusive dressing. The remaining drug was removed and the treated skin area of both groups was stripped with adhesive tape. Total urine and faeces were collected in portions up to 3 weeks after the experiment and blood samples were taken at intervals for 3 weeks. Radioactivity was measured in the skin strippings and in the urine, faeces and plasma samples. The intact drug was assessed in the plasma samples. Using mass balance techniques it could be shown that a mean of 92% (range: 84-101%) of the applied radioactivity could be recovered. Small differences in the absorption and elimination of the radioactivity were observed between the two groups but they were not statistically significant (alpha = 0.05). Therefore data from the two groups were pooled. Elimination of drug and drug-related material from the body was very slow. During the 3-week collection period, a mean of 7% (range: 3.8-10.2%) of the dose was excreted in urine and faeces. Another 0.9-3.3% of the dose was retained in the upper layers of the skin as shown by the skin strippings after treatment. Levels of radioactivity and of intact drug in plasma were below the detection limit of 0.5 ng-equiv./ml, respectively. Present data suggest that mean percutaneous absorption of amorolfine following topical application of the 0.25% cream formulation should not exceed 8-10% of the dose applied.