利多卡因缓释胶丸皮下植入的药代动力学

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。

The pharmacokinetic study of lidocaine sustained release preparation by subcutaneous embedding

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.