替硝唑对盆腔炎模型大鼠血浆和子宫组织中左氧氟沙星药动学的影响

Effects of Tinidazole on the Pharmacokinetinetics of Levofloxacin in Plasma and Uterine Tissue of Pelvic Inflammatory Model Rats

目的:探讨替硝唑对盆腔炎模型大鼠血浆和子宫组织中左氧氟沙星(LVFX)药动学的影响。方法:取雌性大鼠,复制慢性盆腔炎模型,将模型大鼠随机分为实验组(替硝唑溶液100 mg/kg+乳酸LVFX混悬液80 mg/kg)和对照组(乳酸LVFX混悬液80mg/kg),每组48只,建模第4天ig相应药物,分别于给药后0.25、0.5、1、1.5、2、4、8、12 h各处死6只大鼠,采集血浆和子宫,以环丙沙星为内标,采用高效液相色谱法测定血浆和子宫组织中LVFX浓度,DAS 2.0软件计算药动学参数。结果:实验组和对照组大鼠血浆和子宫组织的药-时曲线均符合二室模型,主要药动学参数血浆c_(max)分别为(15.17±0.87)、(14.94±0.46)μg/ml,子宫组织c_(max)分别为(14.18±1.20)、(11.86±0.84)μg/ml;血浆t_(max)分别为(1.42±0.20)、(1.5±0.01)h,子宫组织t_(max)分别为(1.25±0.27)、(1.17±0.26)h;血浆t_(1/2β)分别为(7.69±2.61)、(7.32±2.80)h,子宫组织t_(1/2β)分别为(7.95±5.29)、(9.16±3.00)h;血浆AUC_(0-12 h)分别为(52.65±6.07)、(51.15±3.53)μg·h/ml,子宫组织AUC_(0-12 h)分别为(52.92±5.87)、(42.59±3.91)μg·h/ml;血浆AUC_(0-∞)分别为(61.27±7.93)、(58.86±4.58)μg·h/ml,子宫组织AUC_(0-∞)分别为(60.64±7.20)、(47.41±4.75)μg·h/ml;血浆CL/F分别为(1.37±0.26)、(1.35±0.10)L/(kg·h),子宫组织CL/F分别为(1.32±0.16)、(1.67±0.17)L/(kg·h)。两组大鼠子宫组织的c_(max)、AUC_(0-12 h)、AUC_(0-∞)和CL/F差异有统计学意义(P<0.05)。结论:替硝唑可明显提高LVFX在盆腔炎模型大鼠子宫组织中的吸收,降低其消除率;其对血浆中LVFX的吸收几乎无影响。

OBJECTIVE： To investigate the effects of tinidazole on the pharmacokinetinetics of levofloxacin （LVFX） in plasma and uterine tissue of pelvic inflammatory model rats. METHODS： Female rats were selected to establish chronic pelvic inflamma- tion model. Those model rats were randomly divided into experimental group （tinidazole 100 mg/kg＋lactic acid LVFX suspension 80 mg/kg） and control group （lactic acid LVFX suspension 80 mg/kg）, with 48 rats in each group. They were given relevant medicine intragastrically 4th day after modeling. 6 rats were respectively sacrificed 0.25, 0.5, 1, 1.5, 2, 4, 8 and 12 h after medication. The plasma and uterine samples were collected. Using ciprofloxacin as internal standard, the concentrations of LVFX in plasma and uterine tissue were detected by HPLC, and the pharmacokinetic parameters were calculated with DAS 2.0 software. RESULTS： Plasma concentration-time curves of LVFX in plasma and uterine tissue of rats in experimental group and control group both fit the two-compartment model. The main pharmacokinetics parameters as follows as CMAx were （15.17 ±0.87） vs. （14.94 ± 0.46） μg/ml for plasma, （14.18± 1.20） vs. （11.86±0.84） μg/ml for uterine tissue; tmax were （1.42±0.20） vs. （1.5±0.01） h for plasma, （1.25 ±0.27） vs. （1.17±0.26） h for uterine tissue; t1/2β were （7.69 ± 2.61） vs. （7.32 ±2.80） h for plasma, （7.95± 5.29） vs. （9.16 ± 3.00） h for uterine tissue; AUC0-12h were （52.65 ± 6.07） vs. （51.15 ± 3.53）μg.h/ml for plasma, （52.92 ± 5.87） vs. （42.59 ± 3.91） μg.h/ml for uterine tissue; AUC0-∞ were（61.27 ± 7.93） vs.（58.86 ± 4.58） μg.h/ml for plasma, （60.64 ± 7.20） vs. （47.41 ± 4.75）μg.h/ml for uterine tissue; CL/F were （1.37± 0.26） vs. （1.35 ± 0.10） L/（kg.h） for plasma, （1.32 ± 0.16） vs. （1.67 ± 0.17） L/（kg. h） for uterine tissue. There were statistical significance in Cmax, AUC0-12 h, AUC0-∞ and CL/F of uterine tissue between 2 groups （P〈0.05）. CONCLUSIONS： Tinidazole can obviously increase the distribution of LVFX in the uterine tissue of pelvic inflammatory model rats, reduce the elimination rate but has no effect on the distribution of LVFX in plasma.