SPINAL CONTROLLED DELIVERY OF BUPIVACAINE FROM DL-LACTIC ACID OLIGOMER MICROSPHERES

Bupivacaine-loaded microspheres made from DL-polylactic acid oligomers of different molecular weights (MW 2000 and 9000 g/mol, named PLA 200 0 and PLA 9000, respectively) which displayed different in vitro relea se profiles were administered via the spinal route to rabbits. In comp arison to the drug administered as a solution (2 mg as equivalent base ), PLA 2000 and PLA 9000 microspheres (10 mg as equivalent base) led t o a slower uptake of the drug in the systemic circulation, as suggeste d by the mean maximal plasma concentrations: 326 +/- 81, 321 +/- 57 an d 64 +/- 54 ng/mL, respectively. Pharmacodynamic evaluation of the ane sthetic action, by means of intensity and time course of motor blockad e, indicated a sustained release. In comparison to the drug solution, the PLA 2000 microspheres led to an increase duration of median maxima l blockade (172 min versus 44.5 min). The PLA 9000 microspheres failed to reach maximal blockade as a result of a too low release rate.