氢化可的松对酮康唑经大鼠皮肤透过性的影响  

Effect of hydrocortisone on the percutaneous penetration of ketoconazole via rat skin

作　　者：苏碧雅[1] 李国锋[1] 熊璐琪[1] 赵博欣[1] 

机构地区：[1]南方医科大学南方医院药学部,广东广州510515

出　　处：《中国药理学通报》2012年第5期705-709,共5页Chinese Pharmacological Bulletin

基　　金：广东省自然科学基金资助项目(No 9151008901000223);广东省科技计划项目资助项目(No 2008B060600068)

摘　　要：目的研究氢化可的松对酮康唑经大鼠皮肤透过性的影响。方法将12只♂Wistar大鼠随机分为两组,每组6只,分别设置为空白乳膏组和氢化可的松乳膏组,大鼠剃除腹部的毛后分别涂空白乳膏和氢化可的松乳膏,每天1次,连续给药两周(2 g·d-1)。给药结束后取下所有大鼠的腹部皮肤,采用改良的Franz扩散池法比较酮康唑乳膏经两组大鼠腹部皮肤的透过性差异,采用HPLC法检测样品中酮康唑的浓度,将浓度换算得到渗透速率。结果酮康唑乳膏经氢化可的松组大鼠腹部皮肤和空白乳膏组大鼠腹部皮肤的渗透速率分别为(0.403+0.026)和(0.730+0.042)μg·cm-2·h-1,两组实验结果差异有显著性(P<0.01)。结论♂Wistar大鼠腹部皮肤连续使用氢化可的松两周后,可能对皮肤组织产生了影响,从而引起酮康唑经皮透过的改变,导致酮康唑经皮透过量减少,渗透速率降低。这一结果提示,患者在使用氢化可的松乳膏后再使用其他经皮给药制剂时可能需考虑调整剂量。Aim To examine the effect of hydrocortisone on the percutaneous penetration of ketoconazole via rat skin.Methods Male Wistar rats were random-ly divided into two groups： control group and hydro cortisone（HC） group while each group contained 6 rats.All rat abdomen was shaved and applicated blank cream or hydrocortisone cream for two weeks（2 g·d-1）.Then the abdominal skin was cut to carry out an in vitro penetration experiment on an improved Franz diffusion cells,and phosphate buffer（PBS,pH 7.4） contained 10% ethanol was used as receptor solution.The samples were analyzed by HPLC,and then the penetrating rate was calculated.Results The penetrating rate of HC and control group was 0.403±0.026 and 0.730±0.042（μg·h-1·cm-2）（n=6）respectively.There was significant difference between the control and the HC group（P0.01）.Conclusions After administration of hydrocortisone for two weeks,the rat skin goes through a pathological change,which is closely interrelated with the decrease of the permeation of ketoconazole.This study suggests that it is vital to focus on the dose of some drugs which are used after administration of hydrocortisone.

关 键 词：氢化可的松 Franz 皮肤 HPLC 酮康唑 渗透速率 

分 类 号：R-332[医药卫生] R322.99