复方盐酸萘替芬乳膏对离体豚鼠皮肤的透皮吸收研究

Transdermal Absorption of Compound Naftifine Hydrochloride Cream in Guinea Pigs in Vitro

目的:研究复方盐酸萘替芬乳膏对离体豚鼠皮肤的透皮作用及皮肤组织中的药物浓度。方法:采用静态渗透室装置,皮片涂不同浓度盐酸萘替芬、酮康唑单一及复方乳膏制剂(盐酸萘替芬1%、2%、4%,酮康唑0.25%、0.5%、1%)后36h内不同时间(6、12、24、36h)取样,采用高效液相色谱法测定样品中及皮肤组织中盐酸萘替芬、酮康唑浓度。结果:盐酸萘替芬、酮康唑经离体豚鼠皮的透过率随时间的延长而缓慢增加。36h时,高浓度复方制剂中盐酸萘替芬、酮康唑经离体豚鼠皮的平均透过率分别为(9.3±8.6)×10-3%、(1.39±0.20)%;豚鼠皮中二者浓度分别为(29.81±12.16)、(60.76±5.47)μg.g-1。结论:复方盐酸萘替芬乳膏局部皮肤给药36h后,药物在皮肤组织中浓度较高,表明其透过皮肤吸收较少。

OBJECTIVE： To study the permeability of compound naftifine hydrochlride cream across guinea pigs＇ skin in vitro and to determine its concentration in skin tissues of guinea pigs. METHODS： A static glass diffusion cell system was used. Samples were taken at 6, 12, 24, and 36 h respectively after applying free skin grafts with naftifine hydrochloride （1%, 2% and 4%）, ketoconazole and its compound cream （0.25%, 0.5%, and 1%） . The concentrations of naftifine hydrochlride and ketoconazole in the samples and skin tissues were determined by HPLC. RESULTS： The permeability of naftifine hydrochlride and ketoconazole across the skins of guinea pigs increased time - dependently. The mean permeation rates of naftifine hydrochlride and ketoconazole in high concentration compound creams across skins of guinea pigs at 36 h were （9.3± 8.6） × 10^-3% and （1.39±0.2）%, respectively, and the concentrations of the two in the skins of guinea pigs were （29.81± 12.16） μg · g ^-1 and （60.76± 5.47） μg · g ^-1 respectively. CONCLUSION： The high drug concentration detected in the skin tissues at 36 h after local application of compound naftifine hydrochloride cream suggests its low transdermal permeability.