Spinal biopharmaceutics of bupivacaine and lidocaine by microdialysis after their simultaneous administration in rabbits.
The aim of the present study was to determine the intrathecal bioavailability of a mixture of lidocaine and bupivacaine in a rabbit model of spinal anesthesia by using the microdialysis technique. Catheter and microdialysis probe were inserted under control of the view either in the epidural or in the intrathecal space. First, the epidural disposition of the mixture of bupivacaine and lidocaine was studied after epidural administration. Then, the intrathecal and plasma dispositions of bupivacaine and lidocaine were investigated following intrathecal or epidural administration. The epidural clearance of bupivacaine was higher than that of lidocaine, suggesting a more significant uptake of bupivacaine into the systemic circulation and/or into the CSF. The intrathecal bioavailability of bupivacaine and lidocaine was 12.3 and 17.9%, respectively, while it was 5.5 and 17.7% following the separate administration of each agent [Clément, R., Malinovsky, J.M., Le Corre, P., Dollo, G., Chevanne, F., Le Verge, R., 1999. Cerebrospinal fluid bioavailability and pharmacokinetics of bupivacaine and lidocaine following intrathecal and epidural administrations in rabbits using microdialysis. J. Pharmacol. Exp. Ther. 289, 1015-21]. After intrathecal administration, a decrease in C(max) and AUC values was observed for bupivacaine in comparison with the separate administration. Moreover, after epidural administration, the systemic resorption was slower and lower, especially for bupivacaine. Such a reduction in the systemic absorption of bupivacaine might increase its intrathecal bioavailability, resulting from a vasoconstrictor effect of lidocaine reducing the systemic absorption of bupivacaine from the epidural space leading to an increase of its extent of absorption through meninges into CSF although its absorption rate was not modified.
Clément
R
R
Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, 35043 Cedex, Rennes, France. galenic@univ-rennes1.fr
Malinovsky
J
J
Le Corre
P
P
Dollo
G
G
Chevanne
F
F
Le Verge
R
R
D000775:Anesthesia, Spinal; D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D001682:Biological Availability; D002045:Bupivacaine / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D005260:Female; D007278:Injections, Spinal; D008012:Lidocaine / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D017551:Microdialysis; D011817:Rabbits; D013116:Spinal Cord / Q000378:metabolism
D000779:Anesthetics, Local; D008012:Lidocaine; D002045:Bupivacaine