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 2000 and PLA 9000, respectively) which displayed different in vitro release profiles were administered via the spinal route to rabbits. In comparison to the drug administered as a solution (2 mg as equivalent base), PLA 2000 and PLA 9000 microspheres (10 mg as equivalent base) led to a slower uptake of the drug in the systemic circulation, as suggested by the mean maximal plasma concentrations: 326 +/- 81, 321 +/- 57 and 64 +/- 54 ng/mL, respectively. Pharmacodynamic evaluation of the anesthetic action, by means of intensity and time course of motor blockade, indicated a sustained release. In comparison to the drug solution, the PLA 2000 microspheres led to an increase duration of median maximal 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.
Le Corre
P
P
Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes I, France.
Estèbe
J P
JP
Chevanne
F
F
Mallédant
Y
Y
Le Verge
R
R
D000818:Animals; D001702:Biopharmaceutics; D002045:Bupivacaine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D006614:Hindlimb / Q000294:innervation / Q000502:physiology; D007278:Injections, Spinal; D007773:Lactates; D019344:Lactic Acid; D008297:Male; D008863:Microspheres; D008970:Molecular Weight; D009407:Nerve Block; D011817:Rabbits; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D003692:Delayed-Action Preparations; D007773:Lactates; D019344:Lactic Acid; D002045:Bupivacaine