利多卡因缓释胶丸皮下植入的药代动力学

The pharmacokinetic study of lidocaine sustained release preparation by subcutaneous embedding

目的：研究利多卡因缓释胶丸（ＬＳＲＰ）在兔和大鼠体内的药代动力学。方法：运用高效液相色谱法（ＨＰＬＣ）测定ＬＳＲＰ在血浆和组织中的浓度。结果：发现兔皮下植入ＬＳＲＰ（２０，４０，８０ｍｇ·ｋｇ－１）后，血浆药物浓度—时间曲线符合缓释制剂的一室开放模型。３种剂量的ＬＳＲＰ吸收半衰期Ｔａ１／２均较利多卡因注射液（ＬＴ，１０ｍｇ·ｋｇ－１，ｓｃ）明显延长。３种剂量ＬＳＲＰ的峰浓度（Ｃｍａｘ）分别为０．２４±０．０９，１．２５±０．２３，５．６５±０．１０ｍｇ·Ｌ－１，而ＬＩ（１０ｍｇ·ｋｇ－１，ＳＣ）的Ｃｍａｘ为２．１８±０．３２ｍｇ·Ｌ－１。４０ｍｇ·ｋｇ－１ＬＳＲＰ经大鼠皮下植入后，在局部皮下组织中利多卡因浓度明显高于血浆、脑、心、肝和肾组织中浓度，并在给药后４８ｈ仍能维持在１．１８μｇ·ｇ－１水平。结论：ＬＳＲＰ经皮下植入后的缓释效果明显。提示ＬＳＲＰ能延长利多卡因的局麻、镇痛作用，并可能减轻其全身毒性。

AIM: To investigate the pharmacokinetics of lidocaine substainedrelease pellet (LSRP) in rabbits and rats. METHOD: The concentrations in plasma and other tissues of LSRP were detected by HPLC. RESULTS: It was found that the characteristics of the plasma drug concentrationtime curve fit the one compartment open model of sustainedrelease preparation after subcutaneous embedding of LSRP(20,40,80 mg·kg-1) to rabbits. The absorption half times (Ta 1/2) of 3 doses of LSRP were significantly longer than that of lidocaine injection (LI) (P<001). The Cmax of 20, 40, 80 mg·kg-1 of LSRP was 024±009,125±023,565±010 mg·L-1 respectively, and the Cmax of LI (10 mg·kg-1,sc) was 218±032 mg·L-1. After administration of 40 mg·kg-1 of LSRP in rats, the concentration in local subcutis was significantly higher than that in brain, heart, liver and kidney, and it could be 118 μg·g-1 at 48 h after administration. CONCLUSION: The sustainedrelease effect of LSRP by subcutaneous embedding is very effective, which indicates that LSRP can prolong the local aneasthetic and analgesic effects of lidocaine and reduce the systemic toxic reaction.