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目的:比较左氧氟沙星静脉给药在正常及肺炎大鼠肺组织中的药动学差异。方法:取SD雄性大鼠24只分为肺炎组及正常组;肺炎组大鼠予建立肺炎链球菌模型,模拟左氧氟沙星人体400 mg/d静脉给药;采用微透析技术对两组大鼠的血液及肺组织同步取样,分别测定其游离左氧氟沙星组织中浓度。结果:(1)静脉给药后,正常组大鼠肺组织游离药物浓度始终低于血药浓度,左氧氟沙星在肺组织中的平均穿透率(PR)为0.47±0.11,而肺炎组大鼠自20min后,肺组织药物浓度与血药浓度相近,PR为1.011 1±0.21(P<0.001);(2)左氧氟沙星在正常组大鼠血液中的消除半衰期(t_(1/2)为(1.04±0.81)h,平均驻留时间(MRT)为(1.76±0.72)h,而在肺炎组大鼠血液中分别为(3.83±0.93)h和(4.49±1.56)h,两组数据经比较其差异有统计学意义(P<0.05),但峰浓度(c_(max))及曲线下面积(AUC)经比较其差异有统计学意义(P<0.05);(3)与正常组大鼠相比,左氧氟沙星在肺炎组大鼠肺组织中c_(max)和AUC_(0~∞)显著增高,即(15.90±5.45)mg/L vs(28.08±9.88)mg/L和(13.20±2.82)mg/(h·L)vs(56.21±18.11)mg/(h·L)(均P<0.05);t_(1/2)和MRT明显延长,即(0.86±0.58)h vs(3.88±1.24)h和(2.16±1.07)h vs(4.80±1.79)h(均P<0.05)。结论:左氧氟沙星静脉给药后在肺炎组大鼠肺组织中的游离药物浓度及AUC值显著升高,穿透率明显高于正常组大鼠,可达到清除肺炎链球菌的有效浓度;感染者(肺炎组)局部组织中所获得的药动学参数比正常者(正常组)更有意义。
Objective: To compare the pharmacokinetics of levofloxacin intravenously in normal and pneumonia rat lungs. Methods: Twenty-four male Sprague-Dawley rats were divided into pneumonia group and normal group. The pneumonia group was established with Streptococcus pneumoniae model to simulate levofloxacin 400 mg / d intravenously. And lung tissue simultaneously sampling, respectively, the concentration of free levofloxacin was measured. Results: (1) After intravenous administration, the concentration of free drug in the lung tissue of rats in the normal group was always lower than that in the plasma. The average penetration rate (PR) of levofloxacin in the lung tissue was 0.47 ± 0.11, After 20min, the concentration of drug in lung tissue was similar to that in plasma, with a PR of 1.011 1 ± 0.21 (P <0.001). (2) The half-life of levofloxacin in the blood of normal rats was (1.04 ± 0.81) h, and the mean residence time (MRT) was (1.76 ± 0.72) h in the pneumonia group and (3.83 ± 0.93) h and (4.49 ± 1.56) h in the pneumonia group, respectively (P <0.05), but the peak concentration (c_ (max)) and area under the curve (AUC) were statistically significant (P <0.05); (3) Compared with the normal group (15.90 ± 5.45) mg / L vs (28.08 ± 9.88) mg / L and (13.20 ± 2.82) mg / L, respectively) in the lung tissue of the pneumonia group, levofloxacin significantly increased in the lung tissue of the pneumonia group, (0.56 ± 0.58) h vs (3.88 ± 1.24) h (h · L) vs (56.21 ± 18.11) mg / (h · L) (all P <0.05) And (2.16 ± 1.07) h vs (4.80 ± 1.79) h respectively (all P <0.05) .Conclusion: After intravenous administration of levofloxacin, the free drug in the lung tissue of pneumonia rats Degree and AUC increased significantly, the penetration rate was significantly higher than the normal group of rats, to clear the effective concentration of Streptococcus pneumoniae; infected patients (pneumonia group) local tissue obtained pharmacokinetic parameters than normal (normal Group) makes more sense.