A dose-response study of epidural liposomal bupivacaine in rabbits

Liposomes are drug delivery systems used to prolong local effects of bupiva caine. We studied the relationships between motor and hemodynamic changes a nd epidural doses of plain bupivacaine (P) and liposomal bupivacaine (L) in rabbits equipped with chronical lumbar epidural and femoral arterial cathe ters. Liposomal (phosphatidylcholine-cholesterol) suspensions contained 20 mg ml(-1) of lipid, and different doses of bupivacaine (Lipo 7.5 = 7.5-; Li po 3.7 = 3.75-; Lipo 2.5 = 2.5-; Lipo 1.2 = 1.25-; and Lipo 0.7 = 0.65-mg o f bupivacaine per mi). Forty rabbits were randomly assigned to five groups to receive epidural anesthesia (1 mi) as follows: Groups I to V received 0. 65 to 7.5 mg of bupivacaine as P then as L. Release rate of bupivacaine fro m liposome was significantly slower using Lipo 3.7 than after Lipo 2.5 (T-d was 3.9 h and 1.7 h respectively). Increasing the doses of L and P resulte d in faster onset time for complete motor blockade and in a prolonged durat ion of motor effects. Liposomal formulation appears to be a powerful delive ry system to prolong the motor effects of bupivacaine since E-50 was lower and E-max higher than after the use of plain solution (E-50 4.49 +/- 1.81 m g and E-max 152 +/- 40 min for P; and E-50 2.61 +/- 0.23 mg and E-max 202 /- 9 min for L). Hemodynamic changes were linearly related to doses of bupi vacaine injected. The best bupivacaine-to-lipid ratio to prolong motor effe cts using our model was 3.75 mg and 20.0 mg respectively (Lipo 3.7). (C) 19 99 Elsevier Science B.V. All rights reserved.