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 bioavailabili ty of a mixture of lidocaine and bupivacaine in a rabbit model of spinal an esthesia by using the microdialysis technique. Catheter and microdialysis p robe were inserted under control of the view either in the epidural or in t he intrathecal space. First, the epidural disposition of the mixture of bup ivacaine and lidocaine was studied after epidural administration. Then, the intrathecal and plasma dispositions of bupivacaine and lidocaine were inve stigated following intrathecal or epidural administration. The epidural cle arance 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 sepa rate administration of each agent [Clement, R., Malinovsky, J.M., Le Corre, P., Dollo, G., Chevanne, F., Le Verge, R., 1999. Cerebrospinal fluid bioav ailability and pharmacokinetics of bupivacaine and lidocaine following intr athecal and epidural administrations in rabbits using microdialysis. J. Pha rmacol. Exp. Ther. 289, 1015-21]. After intrathecal administration, a decre ase 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 in trathecal bioavailability, resulting from a vasoconstrictor effect of lidoc aine reducing the systemic absorption of bupivacaine from the epidural spac e Leading to an increase of its extent of absorption through meninges into CSF although its absorption rate was not modified. (C) 2000 Elsevier Scienc e B.V. All rights reserved.