Systemic absorption and safety of multiple doses of topical tazarotene/betamethasone dipropionate cream in healthy subjects and patients with psoriasis / 中华皮肤科杂志

ABSTRACT

Objective:To evaluate the systemic absorption and safety of multiple doses of topical tazarotene/betamethasone dipropionate cream in healthy subjects and patients with psoriasis.Methods:From September 2008 to April 2009, 12 healthy subjects collected from Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College were randomly and equally divided into tazarotene 0.15%/betamethasone dipropionate 0.15% cream group and tazarotene 0.2%/betamethasone dipropionate 0.2% cream group; these subjects were instructed to apply 0.03 g of the test drug per day on each of the 4 body sites, including the flexor aspects of bilateral forearms, waist and back, for 7 consecutive days, and venous blood samples were obtained before, and 1, 3, 5 and 7 days after the start of drug application. From October 2010 to August 2011, 60 patients with non-cephalic psoriasis collected from the Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College were randomly divided into 3 groups at a ratio of 3∶1∶1, i.e., tazarotene 0.05%/betamethasone dipropionate 0.05% cream group ( n = 36) and tazarotene 0.05% gel group ( n = 12) topically treated with a cream vehicle in the morning and the test drug at night, and betamethasone dipropionate 0.05% cream group ( n = 12) topically treated with the test drug twice a day (once in the morning and again in the evening) ; the treatment lasted 6 consecutive weeks, and venous blood samples were collected before, and 2, 4 and 6 weeks after drug application. Liquid chromatography-tandem mass spectrometry was performed to determine the concentrations of tazarotenic acid and betamethasone in plasma. During the trial, adverse events in the subjects were recorded, routine blood and urine examinations were carried out, and liver and kidney function were evaluated before and after treatment. Results:The plasma concentrations of tazarotenic acid and betamethasone in the 12 healthy subjects were below the lower limit of quantitation (0.04 μg/L) after 1-, 3-, 5- and 7-day treatment. After the consecutive treatment, tazarotenic acid and betamethasone were detected in 2 (5.56%) and 4 (11.11%) patients respectively at week 2, 4 or 6 in the tazarotene 0.05%/betamethasone dipropionate 0.05% cream group, and the highest plasma concentrations of tazarotenic acid and betamethasone were 0.112 and 0.201 μg/L respectively; in the betamethasone dipropionate 0.05% cream group, betamethasone was detected in 2 of 12 patients, and the highest plasma concentration of betamethasone was 0.112 μg/L. No test drug-related systemic adverse reactions or laboratory abnormalities were observed in any of the healthy subjects or patients.Conclusion:Multiple doses of topical tazarotene/betamethasone dipropionate cream has advantages of little systemic absorption, no long-term accumulation and good systemic safety.