Effect of Shenkang injection on the cytochrome 2C9 enzyme activity in rats
10.13699/j.cnki.1001-6821.2017.13.020
- VernacularTitle:肾康注射液对大鼠药代动力学及细胞色素2C9酶活性的影响
- Author:
Ze-Na CHANG
1
;
USMAN MUHAMMAD
;
Zhen-Han ZHU
;
Jun-Ping HAN
;
Tian-Ao CHEN
;
Chang-Qing YANG
Author Information
1. 中国药科大学基础医学与临床药学学院
- Keywords:
Shenkang injection;
diclofenac;
4'-hydroxy-dielofenac;
cytochrome P450 2C9;
pharmacokinetic
- From:
The Chinese Journal of Clinical Pharmacology
2017;33(13):1240-1243,1247
- CountryChina
- Language:Chinese
-
Abstract:
Objective Diclofeanc as probe drug to investigate the influence of Shenkang injection on the activity of CYP2C9 enzyme in rats.Methods A total of 24 SD male rats were randomly divided into control group (0.9％ NaCl),low dose (6.7 mL · kg-1),middle dose (13.3 mL· kg-1),high dose (26.6 mL · kg-1) Shenkang injection group,each group 6 rats.The relevant injection was administered by intraperitoneal injection,twice a day for 7 d.On the eighth day before collected the blood plasma samples each group were given relevant injection and all rats were injected with diclofenac (15 mg · kg-1,iv) 1 h after last administration.The orbital blood samples were collected before and 5,15,30,45 min and 1,1.5,2,3,4,6,8,10,12,24 h after diclofenac administration through femoral venous.A sensitive high-performance liquid chromatography method was established to characterize and validate for the determination of plasma concentration of diclofenac and 4'-hydroxy-diclofenac in rats.Pharmacokinetic parameters were calculated with WinNolin 6.1 pharmacokinetic software.Results The area under the concen-tration-time curve (AUC0-24 h) of diclofenac in control group,low,middle and high-dose Shenkang injection group were (21.12±2.88),(25.13 ±8.13),(31.11 ± 11.19),(32.32 ±6.18) mg · h · L-1(P ＞0.05).The AUC0→24h of 4'-hydroxy-diclofenac were (9.79 ±1.12),(7.84 ±2.67),(9.97 ±3.85),(10.39 ±3.38)mg · h · L-1 (P＞0.05).The t1/2 of diclofenac in control group,low,middle and high-dose Shenkang injection group were (6.21 ± 1.78),(7.46 ±2.20),(6.40 ± 1.50),(6.13 ±2.19) h(P ＞0.05).The t1/2 of 4'-hydroxy-diclofenac in control group,low,middle and high-dose Shenkang injection group were (11.53 ±4.31),(30.85 ± 10.52),(23.29 ± 13.09),(22.53 ± 10.95)h(P ＞0.05).There was no statistical significant difference in other pharmacokinetic parameters (P ＞ 0.05).Conclusion Consecutive administration of Shenkang injection may not have an effect on the pharmacokinetic of diclofenac and 4'-hydroxy-diclofenac of typical probe substrates of CYP2C9 in rats.The present study would provide some reference on Shenkang injection have no influence on CYP2C9.
