Background and Aims To study the pharmacokinetic , pharmacodynamic effects and histocompatibility of bupivacaine PLGA microspheres intrathecally in rabbits.

Methods The 12 rabbits were divided randomly into two groups(n=6). One group was injected with bupivacaine solution 5mg/kg intrathecally, the other group was intrathecally injected with bupivacaine PLGA microspheres 5mg/kg. A high performance liquid chromatographic method was developed to determine bupivacaine plasma concentration. A rabbit model for evaluation of spinal anesthesia was presented on the pharmacodynamic study.

Results The Cmax of bupivacaine by intrathecally adminstration with Bupi-PLGA-MS were lower than that with plain bupivacaine injection(P<0.01), Tmax and MRT of Bupi-PLGA-MS were prolonged evidently compared with plain bupivacaine injection(P<0.01).A new spinal administration in rabbits has been established to research the sustained release of Bupi-PLGA-MS in vivo, and a method to evaluate the spinal anaesthetic effect first was set up. The anaesthetic time of bupivacaine microspheres groups were longer than that of plain bupivacaine injection group (P<0.01). The anaesthetic time of different anaesthetic stage by spinal administration with Bupi-PLGA-MS was prolonged compared with that of bupivacaine injection (P<0.01). There was no irritation of Bupi-PLGA-MS to the pinal tissues. The degradation occurred at the surface and the inner of microspheres, moreover, there were remained microspheres matrix after 14days degradation.

Conclusions The incorporation of local anesthetics into injectable PLGA microspheres can be useful in providing prolonged spinal anesthesia effects.