PLASMA-CONCENTRATIONS OF BUPIVACAINE AFTER BRACHIAL-PLEXUS ADMINISTRATION OF LIPOSOME-ASSOCIATED AND PLAIN SOLUTIONS TO RABBITS

Bupivacaine has been associated to multilamellar liposomes with the ai m of altering circulating plasma concentrations a er injection into th e rabbit brachial plexus. Plasma concentrations of bupivacaine have be en compared after admistration of free drug (BP) or bupivacaine associ ated to multilamellar liposomes (BP-MLV) made of phosphatidylcholine a nd cholesterol (molar ratio 4:3). Under light general anaesthesia, one group of six rabbits received an axillary injection of 2.5 mg BP (1 m l, 0.25%, and a second received the same dose of BP-MLV In both groups H-3 bupivacaine was used as a marker. The brachial plexus was located using a nerve stimulator. Injection of the anaesthetic solutions inva riably prevented the motor response of the paw. The arterial plasma co ncentrations of bupivacaine were determined after 5 to 240 min and aft er 24 hr by beta counting. In the MLV population, additional measureme nts were performed after 48 and 72 hr. The two plasma curves showed a plateau (0.2 mug . ml-) which was reached after five minutes in the BP group and after 90 min using BP-MLV In the BP-MLV group, the plasma c oncentrations of bupivacaine were lower during the first ten minutes ( P < 0.05), and higher after 24 hr (P < 0.05). Radioactivity decreased between 4 and 24 hr in the BP group and between one and two days in th e BP-MLV population. It is concluded that elevated plasma drug concent rations were maintained for longer with BP-MLV than with BP. This coul d prolong the action of the local anaesthetic through a slow release.