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A dose-response study of epidural liposomal bupivacaine in rabbits

par Malinovsky, Jean-Marc;Le Corre, Pascal;Meunier, Jean-François;Chevanne, François;Pinaud, Michel;Leverge, Roger;Legros, Franz Jacques
Référence Journal of controlled release, 60, 1, page (111-119)
Publication Publié, 1999-06

Article révisé par les pairs

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Résumé :

Liposomes are drug delivery systems used to prolong local effects of bupivacaine. We studied the relationships between motor and hemodynamic changes and epidural doses of plain bupivacaine (P) and liposomal bupivacaine (L) in rabbits equipped with chronical lumbar epidural and femoral arterial catheters. Liposomal (phosphatidylcholine-cholesterol) suspensions contained 20 mgml-1 of lipid, and different doses of bupivacaine (Lipo 7.5=7.5-; Lipo 3.7=3.75-; Lipo 2.5=2.5-; Lipo 1.2=1.25-; and Lipo 0.7=0.65-mg of bupivacaine per ml). Forty rabbits were randomly assigned to five groups to receive epidural anesthesia (1 ml) as follows: Groups I to V received 0.65 to 7.5 mg of bupivacaine as P then as L. Release rate of bupivacaine from 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 resulted in faster onset time for complete motor blockade and in a prolonged duration of motor effects. Liposomal formulation appears to be a powerful delivery system to prolong the motor effects of bupivacaine since E50 was lower and E(max) higher than after the use of plain solution (E50 4.49±1.81 mg and E(max) 152±40 min for P; and E50 2.61±0.23 mg and E(max) 202±9 min for L). Hemodynamic changes were linearly related to doses of bupivacaine injected. The best bupivacaine-to-lipid ratio to prolong motor effects using our model was 3.75 mg and 20.0 mg respectively (Lipo 3.7). Copyright (C) 1999 Elsevier Science B.V.