Evaluation of human skin tolerance to creams containing tazarotene and betamethasone dipropionate

Abstract

Objective To evaluate skin tolerance to creams containing different concentrations of tazarotene and betamethasone dipropionate in healthy volunteers after single or multiple applications, and to predict potential adverse effects of these creams as well as their degree. Methods Thirty-four healthy volunteers were enrolled in a single-dose trial group, and divided into six subgroups to receive single session of topical treatment with creams containing tazarotene and betamethasone dipropionate both at the concentrations of 0.025%, 0.05%, 0.1%, 0.15%, 0.2% and 0.25% respectively. Another 12 healthy volunteers were enrolled in a multiple-dose trial group, and divided into two subgroups to topically apply creams containing tazarotene and betamethasone dipropionate both at the concentrations of 0.2% and 0.15% , respectively, once a day for 7 consecutive days. General status and subjective feelings of these testees were evaluated, skin reactions at application sites were observed, and routine laboratory examinations(including routine blood test, routine urine test, hepatic and renal function examination)were performed, before and after the application of these creams in both single-and multiple-dose trials. Endogenous cortisol levels were measured before and 7, 14 days after the initial application of the creams, and the amount of drugs percutaneously absorbed into systemic circulation was determined before and 1, 3, 5, 7 days after that in the multiple-dose trial. Results No serious adverse events were found in the study. In the single-dose trial, the testees showed no drug-related adverse reactions or abnormal changes in test patameters after the application of the creams. In the multiple-dose trial, no aberrant skin reaction or self-reported discomfort was noted in any of the testees from day 0 to 7 after the first initial application of the creams, but mild irritation occurred in 5 out of 6 volunteers applying the cream containing 0.2% tazarotene and 0.2% betamethasone dipropionate and in 2 out of 6 volunteers applying the cream containing 0.15% tazarotene and 0.15% betamethasone dipropionate on day 14, with no abnormal drug-related changes in the other test parameters. Conclusions The maximum tolerated concentration of both tazarotene and betamethasone dipropionate is 0.25% when they are topically applied in a combined cream for one session. It is relatively safe to apply the cream containing 0.15% tazarotene and 0.15% betamethasone dipropionate for 7 consecutive days. Key words: Skin; Haman body; External application drugs; Drug tolerance; Tazarotene betamethasone dipropionate cream