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| PK/PD analysis of Qiguiyin Decoction on Levofloxacin against drug- resistant Pseudomonas aeruginosa in semivivo in rats #br# |
| ZHANG Wanqiao1* LI Yanling1* WU Jun2 LIU Qingquan3 XU Guang1 QIN Ming1 JI Li1 MA Qun1 |
1.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China;
2.School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China;
3.Department of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China |
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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.
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