达托霉素在大鼠左右心室中血药浓度的对比研究

Comparison between daptomycin plasma concentration in left ventricle and that in right ventricle of rats

目的利用高效液相色谱-质谱联用法(HPLC-MS)检测达托霉素在大鼠左心室及右心室的血药浓度,进而评估达托霉素对左心感染性心内膜炎(LIE)的治疗效果.方法将35只健康SD大鼠按随机数字表法分为对照组(5只)和达托霉素组(30只),达托霉素组再按给药后0.25、0.5、1、2、4、8h各抽血时间点分为6个亚组,每组5只.对照组给予生理盐水;达托霉素组经尾静脉注射50mg/kg达托霉素.于相应时间点取左心室及右心室血液,利用HPLC-MS测定达托霉素血药浓度;比较不同时间点左心室及右心室中达托霉素血药浓度水平的差异.对照组用于HPLC-MS方法学分析.结果给药后0.25、0.5、1、2、4、8h大鼠左心室及右心室中达托霉素血药浓度(g/L)比较差异均无统计学意义(分别为2.67±0.30比2.77±0.31、1.77±1.27比1.64±0.55、1.35±0.40比1.36±0.41、0.97±0.07比0.92±0.09、0.73±0.16比0.65±0.18、0.07±0.06比0.06±0.05,均P>0.05).结论达托霉素在左心室和右心室中的血药浓度比较差异无统计学意义,推测达托霉素对于LIE可能有同样的治疗效果.

Objective To detect the plasma concentrations of daptomycin in the left ventricle and right ventricle of rats by high-performance liquid chromatography-mass spectrometry(LC-MS/MS), and evaluate the therapeutic effect of daptomycin on left ventricular endocarditis. Methods Thirty-five healthy Sprague-Dawley (SD) rats were divided into a normal saline group (5 rats) and a daptomycin group (30 rats) according to the random number table method. The daptomycin group was subdivided into 6 subgroups according to the times of blood collection (0.25, 0.5, 1, 2, 4, 8 hours), with 5 rats in each subgroup. The normal saline group was given 4 mL/kg normal saline;the daptomycin group was injected with 50 mg/kg daptomycin into the tail vein. The blood samples from left ventricle and right ventricle were extracted at the corresponding time points, the plasma concentrations of daptomycin group were determined by high performance liquid chromatography-mass spectrometry (HPLC-MS) and the differences of left ventricular and right ventricular plasma concentrations were compared at different time points. The plasma in normal saline group was the blank plasma that was used for HPLC-MS methodological evaluation. Results There were no statistical significant differences between the left ventricle and right ventricle in plasma concentrations of daptomycin at 0.25, 0.5, 1, 2, 4, and 8 hours after administration (g/L: 2.67±0.30 vs. 2.77±0.31, 1.77±1.27 vs. 1.64±0.55, 1.35±0.40 vs. 1.36±0.41, 0.97±0.07 vs. 0.92±0.09, 0.73±0.16 vs. 0.65±0.18, 0.07±0.06 vs. 0.06±0.05, respectively all P > 0.05). Conclusion There are no significant differences between the left ventricle and right ventricle in plasma concentrations of daptomycin. It is speculated that daptomycin may have the same therapeutic effect on left endocarditis.