Pharmacokinetics of intrathecally injected bupivacaine PLGA microspheres in rabbits

Objective: To study the pharmacokinetics of bupivacaine PLGA microspheres in rabbits. Methods: Twelve rabbits were randomly divided into groups A and B（n=6）. Rabbits in group A were intrathecally injected with bupivacaine solution（5mg/kg）,rabbits in group B were intrathecally injected with bupivacaine PLGA microspheres（5mg/kg）.High performance liquid chromatography was used to determine the plasma concentration of bupivacaine. Results: In group A,the plasma concentration of bupivacaine reached its peak quickly about 0.5h after subarachnoid space injection,the Cmax was 0.567μg/mL.Then,the plasma concentration of bupivacaine quickly declined and became indetectable within 8h.In group B,the plasma concentration of bupivacaine PLGA microspheres reached its peak 0.5h and 2h,respectively,after injection bupivacaine PLGA microspheres,the Cmax was 0.332 and 0.290μg/mL,respectively.Then,the plasma concentration of bupivacaine PLGA microspheres slowly declined and became stable within 48h（P＜0.05）.The mean retention time（MRT）was significantly longer in group B than in group A（P＜0.05）. Conclusion: Incorporation of local anesthetics into injectable PLGA microspheres has a prolonged spinal anesthesia effect in rabbits.