复方酮康唑软膏的透皮吸收  

Transdermic absorption of compound ketoconazole ointment

作　　者：陈铁锋[1] 余细勇[1] 林曙光[1] 杨敏[1] 江桂芬[1] 钱忆之[1] 

机构地区：[1]广东省心血管病研究所临床药理室,广东广州510080

出　　处：《中国现代应用药学》2003年第2期134-137,共4页Chinese Journal of Modern Applied Pharmacy

摘　　要：目的　研究皮肤用复方酮康唑软膏后其成分酮康唑和丙酸氯倍他索药物的透皮吸收与体内蓄积性。方法　 1 5只新西兰大白兔分为 4 % (高浓度药物组 )、1 % (治疗量药物组 )和基质组 ,每兔皮肤一次性涂药膏 5g/d ,2 4h内收集药时血样。另 1 %用药组连续涂药 7d ,收集每天峰、谷浓度血样。用高效液相色谱法同时测定酮康唑和丙酸氯倍他索血药浓度。结果　 4 %、1 %组酮康唑 2h达峰 ,丙酸氯倍他索 4h达峰 ,两组、两药的峰浓度分别为 0 .1 1± 0 .0 9和 0 .0 6± 0 .0 2mg/L ;0 .0 6± 0 .0 1和0 .0 4± 0 .0 2mg/L。随后两药浓度下降并维持于一个较低水平。连续用药后酮康唑的峰浓度和谷浓度前 4d上升 ,d4是d1的3倍 ,d5、6、7处于平稳状态并呈下降趋势 ,d7分别为d1的 1 .63、1 .69倍 ;丙酸氯倍他索的峰浓度和谷浓度变化趋势类似于酮康唑。结论　复方酮康唑软膏皮肤用药后透皮吸收量很少 。OBJECTIVE AIM To investigate the transdermic absorption levels and cumulative amounts of ketoconazole and clobetasoli propionas after in vitro administration of compound ketoconazole ointment. METHOD Fifteen New Zealand white rabbits were divided into 3 groups: high dose group (4% ointment) therapeutic dose group (1% ointment) and control(matrix) group. Five grams of the ointment was applied on the back skin of each rabbit. For the therapeutic dose group, the ointment was continuously applied, daily for 7 days once per day. The blood samples were collected at varied time, and the concentration of plasma drugs were determinated by high performance liquid chromatography. RESULTS The peak concentrations of ketoconazole were reached at 2h with 0.11±0.09 and 0.06±0.02mg/L for 4% and 1% ointment respectively. The peak concentrations of clobetasoli propionas were reached at 4h with 0.06±0.01 and 0.04±0.02mg/L for 4% and 1% ointment respectively. After continuous multiple administration, the peak and trough concentrations of ketoconazole ascended gradually and reached 3 times that of the first day on the fourth day, but the concentrations tend to steady state, on the fifth, sixth and seventh day, there only 1.63 times peak concentration and 1.69 times rough concentration at seventh day than that in first day. The changed tendency of clobetasoli propionas concentrations were similar to that of ketoconazole.CONCLUSION The amounts of transdermic absorpation were small after applying compound ketoconazole ointment. There was no cumulation in vivo in this ointment.

关 键 词：复方酮康唑软膏 酮康唑 丙酸氯倍他索 透皮吸收 血药浓度 体内蓄积性 

分 类 号：R978.5[医药卫生—药品] R969.1[医药卫生—药学]