论文部分内容阅读
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。
Objective: To study the pharmacokinetics of lidocaine sustained-release capsules (LSRP) in rabbits and rats. Methods: The concentrations of LSRP in plasma and tissue were determined by high performance liquid chromatography (HPLC). RESULTS: After being subcutaneously injected with LSRP (20, 40, and 80 mg · kg -1), the plasma drug concentration-time curve was consistent with the one-compartment open model of sustained-release preparation. The LSRP absorption half-life (Ta1 / 2) of three doses was significantly longer than that of lidocaine injection (LT, 10 mg · kg-1, sc). The peak concentrations of three kinds of LSRPs were 0.24 ± 0.09,1.25 ± 0.23 and 5.65 ± 0.10 mg · L -1, respectively, while LI (10 mg · kg -1, SC ) Cmax was 2.18 ± 0.32mg · L-1.40mg · kg-1LSRP after subcutaneous implantation in rats, the local subcutaneous tissue concentration of lidocaine was significantly higher than plasma, brain, heart, liver and kidney Tissue concentrations, and can maintain the level of 1.18μg · g-1 48h after administration. Conclusion: The sustained-release effect of LSRP after subcutaneous implantation is obvious. This suggests that LSRP prolongs local anesthesia and analgesia of lidocaine and may reduce its systemic toxicity.