摘要
目的:通过与已上市单方他扎罗汀凝胶(tazarotene gel)和二丙酸倍他米松乳膏(betamethasone dipropionate cream)比较,研究新的复方制剂他扎罗汀倍他米松乳膏(tazarotene and betamethasone dipropionate cream,简称"复方")对小型猪经皮给药后的药物吸收以及药物组分间吸收的相互影响。方法:将18只小型猪随机分入复方组、他扎罗汀凝胶组和二丙酸倍他米松乳膏组,每组6只。小型猪按20%的体表面积2 mg·cm-2给予相应组别的药物,并在给药后24 h清除药物。分别于给药前和给药后不同时间点采集血样。高效液相色谱-串联质谱(liquid chromatography-tandem mass spectrometry, LC-MS/MS)法测定血浆中他扎罗汀及其代谢物他扎罗汀酸和/或二丙酸倍他米松及其代谢物倍他米松的浓度。DAS 2.1.1软件进行药代动力学(pharmacokinetic, PK)参数计算并统计分析。结果:复方他扎罗汀倍他米松乳膏与单方他扎罗汀凝胶中的他扎罗汀均不易透过小型猪皮肤到达血液,系统吸收非常低,而复方组血浆中的他扎罗汀及其活性代谢产物他扎罗汀酸较单方组更低;复方他扎罗汀倍他米松乳膏和二丙酸倍他米松乳膏中的二丙酸倍他米松几乎不透过小型猪皮肤到达血液,系统吸收非常低,其中复方组与单方组中二丙酸倍他米松及其代谢产物倍他米松到达血液的量未见明显的差异。结论:复方制剂中他扎罗汀对二丙酸倍他米松的系统吸收未产生相互作用,而二丙酸倍他米松对他扎罗汀的系统吸收产生了有益的相互作用,有利于用药安全。
OBJECTIVE To study system absorption and drug-drug interaction of a new fixed-dose combination of tazarotene and betamethasone dipropionate cream(abbreviated as FDC) in mini-pig after topical administration compared with tazarotene gel and betamethasone dipropionate cream respectively.METHODS 18 minipigs were randomly divided into compound group, tazarotene gel group and betamethasone dipropionate cream group with six mini-pigs in each group. Corresponding drugs were administrated to the dorsa and costal abdomen of mini-pigs with a dose of 2 mg·cm-2(the dosing area was about 20% of body surface area of mini-pig) and were cleaned 24 h after administration. Blood samples were collected before administration and different time points after administration. The plasma concentrations of tazarotene, betamethasone dipropionate and their respective metabolites, tazarotenic acid and betamethasone were all detected by LC-MS/MS. The pharmacokinetic parameters were calculated and analyzed using DAS 2.1.1 software.RESULTS Neither FDC nor tazarotene gel could easily penetrate into blood through the skin of mini-pigs after topical administration, so the systematic absorption of tazarotene was very low. The amounts of tazarotene and tazarotenic acid(metabolite) in the blood of FDC group were less than that of tazarotene gel group. The betamethasone dipropionate in FDC and betamethasone dipropionate cream could hardly penetrate the skin of mini-pigs into blood, so the systematic absorption was also very low. No significant difference of the amounts of betamethasone dipropionate and its metabolite betamethasone in blood was found between the FDC group and betamethasone dipropionate cream group.CONCLUSION In the new FDC, tazarotene had no influence on the system absorption of betamethasone dipropionate, but betamethasone dipropionate had a beneficial influence on the systematic absorption of tazarotene, which was beneficial to the safe use of the drug.
作者
魏峻
陶蕾
李玲珺
钱坤
丁黎
马鹏程
WEI Jun;TAO Lei;LI Ling-jun;QIAN Kun;DING Li;MA Peng-cheng(Department of Materia Medica,In stitute of Dermatology,Chinese Academy of Medical Sciences&Peking Union Medical College,Jiangsu Nanjing 210042,China;De partment of Pharmaceutical Analysis,Chinese Pharmaceutical University,Jiangsu Nanjing 210009,China)
出处
《中国医院药学杂志》
CAS
北大核心
2019年第22期2253-2258,共6页
Chinese Journal of Hospital Pharmacy
基金
国家科技重大专项(重大新药创制)(编号:2010ZX09401-306)
