BIODISTRIBUTION OF LIPOSOME-ASSOCIATED BUPIVACAINE AFTER EXTRADURAL ADMINISTRATION TO RABBITS

After one extradural injection of 0.25% bupivacaine 0.3 ml and H-3-bup ivacaine 0.005 mCi in multilamellar liposomes, no systemic radioactivi ty (plasma, liver, heart muscle) was obtained for 1 h, and the labelli ng was less than that of systemic distribution of plain bupivacaine fo r the following 3 h. In contrast, radioactivity in the lumbar spinal n erves peaked in the first hour and remained higher than that of plain bupivacaine for 4 h. No radioactivity was measured in cerebrospinal fl uid, Small unilamellar vesicles incorporating H-3-cholesterol did not significantly label spinal nerves and central nervous structures indic ating that the mode of action of liposomal bupivacaine did not involve uptake by nerve structures. Rapid uptake of radioactivity by spinal n erves suggested exchange of bupivacaine between liposomes and nerve sh eaths.