Kinetic and dynamic studies of liposomal bupivacaine and bupivacaine solution after subcutaneous injection in rats.

The pharmacodynamics and pharmacokinetics of bupivacaine in solution and in liposome preparations following subcutaneous administration were studied in rats. Multilamellar vesicles entrapping bupivacaine solution were prepared. The local anaesthetic effect was estimated by the tail-flick test in Wistar rats treated with 1 mg bupivacaine in 0.2-mL preparations. Plasma concentrations of bupivacaine were determined by high-performance liquid chromatography. The results showed that both bupivacaine solution and bupivacaine liposomes revealed local anaesthetic effects in the initial tail-flick test (15 min after injection). With bupivacaine liposomes, the duration of action was 5-fold (447+/-28.9 vs 87+/-6.7 min), the maximum possible effect was 2-fold (100+/-0 vs 47.6+/-13%), and the peak plasma concentration (Cmax) was less than one-fifth (0.12+/-0.04 vs 0.65+/-0.04 microg mL(-1)) that with bupivacaine solution. The sensory block effect of bupivacaine solution completely resolved at 90 min, while the plasma concentration of bupivacaine was still more than half the Cmax. Bupivacaine liposomes resulted in a low and relatively constant plasma level (approx. 0.1 microg mL(-1)) and a pronounced local anaesthetic effect throughout the experimental period (> 7 h). In conclusion, bupivacaine liposomes elevated the intensity and prolonged the duration of the local anaesthetic effect of bupivacaine, and suppressed the systemic absorption rate of encapsulated bupivacaine.