Pharmacokinetic of liposome-free and liposome-encapsulated mepivacaine solutions in rats

Objectives: The aim of this study was to observe the pharmacokinetics of liposome-free and liposome-encapsulated mepivacaine formulations injected intra-orally in rats. Methods: Twelve male Wistar rats (Rattus novergicus) were divided into three groups (n=4). The animals received 0.1 ml of the following formulations: 2% mepivacaine with 1:100.000 epinephrine (MVC2% EPI), 3% mepivacaine (MVC3%) and 2% liposome-encapsulated mepivacaine (MVCLUV). Blood samples (0.4 ml) were collected from the cannulated femoral vein and the mepivacaine plasma levels were determined using liquid chromatography–tandem mass spectrometry (LC-MS/MS), at 0, 15, 30, 45, 60, 120, 180, 240, 300, 360 and 420 minutes after the injection. Data were analyzed by using ANOVA and Tukey test (á=5%). Results: None statistically significant difference (p>0.05) were observed between the plasma levels of MVCLUV and MVC2% EPI at all periods of time. The maximum plasma concentration (Cmax) after MVCLUV injection (0.27±0.07 µg/mL) was about six times lower (p<0.05) than MVC3% (1.76±0.93 µg/mL). The area under the curve (AUC0-420) obtained after the injection of MVCLUV (91.55± 24.42 µg-min/mL) was 50% smaller (p<0.05) when compared with the area obtained with MVC3% (228.48± 38.73 µg-min/mL). Cmax (0.41±0.13 µg/mL) and AUC0-420 (95.83± 60.20 µg-min/mL) obtained with MVC2% EPI showed no statistically significant differences (p>0.05) in relation to MVCLUV results. The time to maximum plasma concentration (Tmax) obtained with MVC2% EPI (105.00±57.3 min), MVCLUV (165.00±57.23 min) and MVC3% (120.00±50.00 min) presented no statistically significant differences (p>0.05). Conclusion: The pharmacokinetic of 2% liposome-encapsulated mepivacaine was comparable to the pharmacokinetic of 2% mepivacaine with 1:100.000 epinephrine. Supported by CNPq and FAPESP #2006/00121-9.