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目的 :研究兔经皮给予双氯芬酸钠贴剂的绝对生物利用度和局部组织药物浓度 ,为临床合理用药提供参考。方法 :单剂量给予静脉给药和贴剂 ,采用反相HPLC测定血浆和局部组织中双氯芬酸钠的浓度。结果 :兔表皮给予双氯芬酸钠贴剂的药代动力学参数为 :AUC 2 2 .6 3(μg·h·ml-1) ,t1/2Ka0 .82h ,t1/2Ke8.5 1h ,tmax2 .5 3h ,Cmax1.6 4 (μg·ml-1) ,CL 0 .91(L·h-1) ,Ka 1.15 (h-1) ,Ke0 .12 (h-1) ;静脉给药在兔体内的药代动力学参数为AUC 4 3.85 (μg·h·ml-1) ,t1/2Ke0 .6 0h ,Cmax5 1.17(μg·ml-1) ,CL 0 .4 7(L·h-1) ,Ke1.16 (h-1)。求算得双氯芬酸钠贴剂的绝对生物利用度为 5 1.6 % ,对两种制剂的药代动力学参数进行双单侧t检验 ,均有显著性差异 (P <0 .0 5 )。再对给予贴剂的兔皮肤、肌肉、血浆 3组之间进行LSD检验 ,各组间均有显著性差异 (P <0 .0 5 ) ,皮肤中的药物浓度是血浆的 36 .5倍。结论 :双氯芬酸钠贴剂的Cmax、AUC低于静脉给药 ,但具有达峰时间长和在体内时间长的特点 ,具有长效作用。贴剂的血药浓度较低 ,而局部血药浓度高 ,避免了双氯芬酸钠所形成的不良反应
OBJECTIVE: To study the absolute bioavailability of diclofenac sodium patch and the local tissue drug concentration in rabbits, which may provide a reference for clinical rational drug use. Methods: Intravenous administration and patch preparation were given in single dose, and diclofenac sodium concentration in plasma and local tissues was determined by reverse phase HPLC. Results: The pharmacokinetic parameters of diclofenac sodium patch in rabbits epidermis were: AUC22.63 (μg · h · ml-1), t1 / 2Ka0.82h, t1 / 2Ke8.5 1h, tmax2.53h , Cmax1.64 (μg · ml-1), CL0.91 (L · h-1), Ka 1.15 (h-1), Ke0.12 (h-1) The kinetic parameters were AUC 4 3.85 (μg · h · ml-1), t1 / 2Ke0.60h, Cmax5 1.17 (μg · ml-1), CL0.47 (L · h-1), Ke1. 16 (h-1). The calculated absolute bioavailability of diclofenac sodium patch was 51.6%. There was a significant difference (P <0.05) in the two-sided one-tailed t test for the pharmacokinetic parameters of the two formulations. LSD test was performed on the skin, muscle and plasma of the rabbits given the patch, with significant differences among the groups (P <0.05). The drug concentration in the skin was 36.5 times that of the plasma. Conclusion: Diclofenac sodium patch Cmax, AUC lower than intravenous administration, but with a long time peak and in vivo characteristics of a long-term effect. The plasma concentration of the patch is lower, while the local plasma concentration is high, avoiding the adverse reactions caused by diclofenac sodium