利多卡因凝胶贴膏外敷在家兔皮肤和DRG中药物分布规律

Drug Distribution in Skin and DRG following Lidocaine Cataplasms Application in Rabbits

摘要:

目的：探讨利多卡因凝胶贴膏外敷后在给药部位皮肤和背根神经节(dorsal root ganglion, DRG)中药物分布规律。方法：8周龄雄性家兔20只，体重2.50 ~ 2.75kg，据用药方法和取材时间随机分为4组（每组5只）：皮内注药后12h组（I12组）、皮内注药后24h组（I24组）、利多卡因凝胶贴膏贴敷12h撤药即刻组（P12组）和利多卡因凝胶贴膏贴敷12h撤药后12h组（P24组)。在相应时间点处死家兔立即取脊柱双侧腹背部表皮与真皮组织和C2 ~ L5节段DRG，应用高效液相色谱法(High performance liquid chromatography, HPLC)检测组织中利多卡因药物浓度。结果：P24组和I12组用药侧DRG利多卡因药物浓度均显著高于对侧，但各组对侧皮肤中均未检测到利多卡因而明显低于用药侧；P12组和I12组用药侧皮肤分别高于P24组和I24组，但P24组与I12组无差异；I12组用药侧DRG中利多卡因高于 I24组。相反，P24组却远远高于P12组，而P24组与I12组无差异。结论: 利多卡因凝胶贴膏贴敷后通过逆行转运机制在DRG中有较高的药物浓度。这提示利多卡因凝胶贴膏与皮内注药有相似的作用机制，可通过作用于局部皮肤和DRG两个环节而镇痛。

Abstract:

Objective: To investigate the drug distribution in the skin and dorsal root ganglion (DRG) after application of lidocaine cataplasms in rabbits. Methods: 8-week-old male rabbits,weighing 2.50-2.75 kg,were randomly divided into 4 groups (5 rabbits in each group): group I12, group I24,,group P12 and group P24. The rabbits were sacrificed 12 hours (group I12) or 24 hours (group I24) after 0.4% lidocaine hydrochloride intradermal injection,or immediately (group P12) or 12 hours (group P24) after the withdrawal of 12-hours’ topical lidocaine cataplasms 5% application,and the skin and C2-L5 DRG were collected on both drug application side and contralateral side. The concentration of lidocaine in the tissues was detected by High performance liquid chromatography（HPLC). Results: The lidocaine concentration in drug side DRG in group P24 and group I12 was significantly higher than those in control side, while lidocaine was significantly lower in the contralateral skin of each group than the drug side and was not detected . The lidocaine in the application side skin of group P12 and group I12 was respectively higher than that of P24 group and I24 group, but there was no difference between group P24 and group I12 .The lidocaine concentration of drug side DRG in group I12 was higher than that in group I24; on the contrary, the lidocaine concentration in group P24 was much higher than that in group P12, and there was no difference between group P24 and group I12. Conclusion: There is a higher drug concentration in DRG by retrograde transport mechanism after topical lidocaine cataplasms 5% application for 12 hours,which suggests that lidocaine cataplasms has a similar mechanism as intradermal injection resulting in pain relieve by acting on local skin and DRG.