双氯芬酸钠贴剂绝对生物利用度和局部组织药物浓度研究  

A Study on Absolute Bioavailability and Pharmacokinetics of Sustained-release Diclofenac Sodium Patch

作　　者：林佳亮[1] 王庭贤 苏云驰 曾凡波[1] 金晶[1] 王涛[1] 

机构地区：[1]华中科技大学同济医学院药学院,武汉430030 [2]湖北制药厂 [3]广东省中山市中健药物研究所

出　　处：《中国药师》2004年第11期834-836,共3页China Pharmacist

摘　　要：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 。Objective: To study the absolute bioavailability and drug concentration in local tissue of a long released diclofenac sodium patch.Method: The diclofenac sodium of sustained released patch and intravenous injection were used in rabbits rectum in single dose respectively. The drug concentrations in plasma and local issue were determined by RP HPLC. Result: The pharmacokinetic parameters of sustained released patch were: AUC 22.63 (μg·h·ml -1 ), t 1/2 K a 0.82 h, t 1/2 K e 8.51 h, t max 2.53 h, C max 1.64 (μg·ml -1 ), CL 0.91 (L·h -1 ), K a 1.15 (h -1 ), K e 0.12 (h -1 ); that of intravenous injection were: AUC 43.85 (μg·h·ml -1 ), t 1/2 K a 0.6 h, C max 51.17 (μg·ml -1 ), CL 0.47 (L·h -1 ), K e 1.16 (h -1 ). The absolute bioavailability of the long released patch was 51.6% . The results show significant difference between the two preparations ( P < 0.05 ). Given the patch, the drug concentration in skin is 36.5 times higher than that in plasma. Conclusion: The 2 preparations are not bioequivalent. The patch tested from our lab has long released properties, its drug concentration in plasma is so low as to the adverse reaction can be avoided.

关 键 词：双氯芬酸钠贴剂 高效液相色谱 反相 生物利用度 绝对 药物浓度 局部组织 

分 类 号：R971.1[医药卫生—药品] R965.2[医药卫生—药学]