芪归银方对左氧氟沙星大鼠半体内抗耐药铜绿假单胞菌的PK/PD分析

doi:10.20047/j.issn1673-7210.2022.32.03

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摘要目的通过建立左氧氟沙星（LVFX）单用及LVFX联用芪归银方的药动学/药效学（PK/PD）模型，探索芪归银方对LVFX抗耐药铜绿假单胞菌（PA）的影响。方法雄性Wistar大鼠6~7周龄15只分为3组，每组5只。单用组灌胃0.01 g/ml的LVFX，联用组灌胃1 g/ml生药浓度的芪归银方和0.01 g/ml的LVFX，空白组灌胃同等体积蒸馏水，连续给药5 d。末次给药后0、0.25、0.50、1.00、1.50、2.00、4.00、8.00、12.00和24.00 h眼眶取血，样品处理后进样，采用DAS 2.0软件计算PK参数，含药血清干预耐药PA测定抑菌率，建立半体内PK/PD模型。结果联用组平均滞留时间、达峰时间长于单用组，清除率高于单用组，曲线下面积和最大血药浓度低于单用组（P ＜ 0.05）。联用组血清抑菌率初始值大于单用组，到达最大抑菌率的时间长于单用组（P ＜ 0.05）。单用组及联用组半体内PK/PD模型为E=（63.80×C2.96）/（0.94+C2.96），E=34.72+（57.88×C3.04）/（66.63+C3.04）。结论芪归银方可能通过影响大鼠LVFX血药浓度增强LVFX抗耐药PA的效果。

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	张婉乔1* 李颜伶1* 吴珺2 刘清泉3 徐广1 秦铭1 吉莉1 马群1

关键词 ：芪归银方, 左氧氟沙星, 铜绿假单胞菌, 药动学/药效学模型

Abstract：Objective To explore the effect of Qiguiyin Decoction on Levofloxacin (LVFX) against drug-resistant Pseudomonas aeruginosa (PA) by establishing the pharmacokinetic/pharmacodynamic (PK/PD) model of LVFX alone and LVFX combined with Qiguiyin Decoction. Methods Fifteen male Wistar rats aged 6-7 weeks were divided into three groups, with five rats in each group. The single group was gavaged with 0.01 g/ml LVFX, the combined group was gavaged with 1 g/ml Qiguiyin Decoction and 0.01 g/ml LVFX, and the blank group was gavaged with the same volume of distilled water for five days. Blood was collected from orbit at 0, 0.25, 0.50, 1.00, 1.50, 2.00, 4.00, 8.00, 12.00, and 24.00 h after the last administration. After sample treatment, the PK parameters were calculated by DAS 2.0 software, the bacteriostasis rate of drug-resistant PA was measured with drug-containing serum, and the hemibody PK/PD model was established. Results The mean residence time, peak time of the combine group were longer than those of control group, and clearance rate of the combined group were higher than those of the single group, the area under the curve and the maximum plasma concentration were lower than those of the single group (P ＜ 0.05). The initial value of serum bacteriostasis rate was higher than that of the single group, and the time to reach the maximum bacteriostasis rate in the combined group were longer than that in the single group (P ＜ 0.05). The semivivo PK/PD models of the single group and the combined group were E = (63.80×C2.96)/(0.94 + C2.96) and E = 34.72 + (57.88×C3.04)/(66.63 + C3.04). Conclusion Qiguiyin Decoction may enhance the effect of LVFX against PA by affecting LVFX blood drug concentration in rats.

Key words： Qiguiyin Decoction Levofloxacin Pseudomo- nas aeruginosa Pharmacokinetics/pharmacodynamics model

基金资助:国家自然科学基金资助项目（81873127）。

通讯作者: 马群（1971.7-），女，博士，研究员，博士生导师；研究方向：中药复方干预细菌耐药的作用机制。

作者简介: 张婉乔（1997.2-），女，硕士；研究方向：中药复方干预细菌耐药的作用机制。李颜伶（1996.9-），女，北京中医药大学中药学院2020级中药分析学专业在读硕士研究生；研究方向：中药复方干预细菌耐药的作用机制。 *具有同等贡献

引用本文:

张婉乔1* 李颜伶1* 吴珺2 刘清泉3 徐广1 秦铭1 吉莉1 马群1. 芪归银方对左氧氟沙星大鼠半体内抗耐药铜绿假单胞菌的PK/PD分析[J]. 中国医药导报, 2022, 19(32): 14-17.
ZHANG Wanqiao1* LI Yanling1* WU Jun2 LIU Qingquan3 XU Guang1 QIN Ming1 JI Li1 MA Qun1. PK/PD analysis of Qiguiyin Decoction on Levofloxacin against drug- resistant Pseudomonas aeruginosa in semivivo in rats #br#. 中国医药导报, 2022, 19(32): 14-17.

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