双氯芬酸钠贴剂相对生物利用度与局部组织药物浓度测定

A Study on Relative Bioavailability and Drug Concentration in Local Tissues of Diclofenac Sodium Patch

目的研究兔经皮给予双氯芬酸钠贴剂的相对生物利用度和局部组织药物浓度,为临床用药提供参考。方法单剂量给予贴剂和凝胶剂,采用反相高效液相色谱法测定血浆和局部组织中的双氯芬酸钠浓度。结果兔表皮给予双氯芬酸钠贴剂的药动学参数如下。AUC:22.63μg.h.mL-1,t1/2Ka:0.82 h,t1/2Ke:8.51 h,tm ax:2.53 h,Cm ax:1.64μg.mL-1,CL/F(s):1.52 L.h-1,Ka:1.15 h-1,Ke:0.12 h-1;凝胶剂在兔体内的药动学参数为AUC:13.07μg.h.mL-1,t1/2Ka:0.27 h,t1/2Ke:1.92 h,tm ax:0.88 h,Cm ax:1.45μg.mL-1,CL/F(s):1.71 L.h-1;Ka:2.62 h-1,Ke:0.37 h-1,求算得双氯芬酸钠贴剂的相对生物利用度为173.14%。对2种制剂的药动学参数进行双侧t检验,均差异有显著性(均P<0.05)。再对给予贴片和凝胶剂的兔皮肤、关节腔、血液3组之间进行LSD检验,各组差异有显著性,给予贴剂的皮肤中药物浓度是血浆的36.5倍,给予凝胶剂的皮肤中药物浓度是血浆的18.68倍。结论双氯芬酸钠贴片的Cm ax高于双氯芬酸钠凝胶外擦给药,贴片的AUC大于凝胶给药的AUC,但具有达峰时间长和在体内时间长的特点,具有长效作用,贴片的生物利用度优于凝胶。

Objective To study the relative bioavailability and drug concentration in local tissues of dielofenac sodium patch, which provides suggestions for the clinical use. Methods The diclofenac sodium of sustained-release patch and gel was given to rabbits via epidermly in a single dose respectively. The drug concentration in plasma and local tissues were determined by RP-HPLC. Results The pharmacokinetic parameters of sustained-released patch given epidermly were AUC：22.63μg·h·mL^-1,t1/2Ke：0.82h,t1/2Ke：8.51h,tmax：2.53h,Cmax：1.64μg·h·mL^-1,CL/F（S）：1.52L·h^-1,Ka：1.15h^-1,Ke：0.12h^-1 ;those of gel were： AUC：13.07μg·h·mL^-1,t1/2Ke：0.27h,t1/2Ke：1.92h,tmax：0.88h,Cmax：1.45μg·h·mL^-1,CL/F（S）：1.71L·h^-1;Ka：2.62h^-1,Ke：0.37h^-1,the relative bioavailability of the long-released patch was calculated as 173.14%. The results showed significant difference between the two preparations by t test （P 〈 0.05 ）. LSD test was conducted among parameters of the patch and gel from skin, articular cavity and blood, respectively, significant variations between groups were showed. Given the patch ,the drug concentration in skin is 36.5 times higher than that in plasma. Given the gel, the drug concentration in skin is 18.68 times higher than that in plasma. Conclusion Cmax and AUC of the patch were higher than those of the gel by external use. But the patch shows long peak time and long-released properties, and the bioavailability of the patch is better than that of the gel.