Influence of ceftriaxone on pharmacokinetics, anticoagulation andantithrombotic effects of phenolic acids from Danhong injection in rats
10.16438/j.0513-4870.2018-0984
- VernacularTitle:头孢曲松改变丹红注射液酚酸类成分在大鼠体内药动学行为和抗凝血抗血栓药效的研究
- Author:
Qian ZHANG
1
,
2
;
Wen-zheng JU
3
;
Jian-ming GUO
1
;
Jian-ping LI
1
;
Yi YAO
3
;
Zhi-shu TANG
4
;
Bu-chang ZHAO
5
;
Jin-ao DUAN
1
Author Information
1. Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources, Nanjing University of Chinese Medicine, Nanjing 210046, China
2. The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
3. The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
4. Shaanxi University of Traditional Chinese Medicine, Xianyang 712000, China
5. Buchang Pharma, Xi’an 710000, China
- Publication Type:Research Article
- Keywords:
Danhong injection;
ceftriaxone sodium;
herb-drug interaction;
pharmacokinetics;
antithrombotic effect;
anticoagulation;
antiplatelet
- From:
Acta Pharmaceutica Sinica
2019;54(4):701-709
- CountryChina
- Language:Chinese
-
Abstract:
Danhong injection (DHI) and ceftriaxone sodium were used in combination based on their experimental uses in clinic. This study was designed to investigate the impact of ceftriaxone on pharmacokinetics and pharmacodynamics of the phenolic acids from DHI. After administration of DHI for 7 d, ceftriaxone (CFTX) was combined with DHI for the next 7 d in adult male Sprague-Dawley (SD) rats. All the drugs were administered through caudal vein. UHPLC-TQ-MS was applied in determining the plasma concentration of p-coumaric acid (p-CA), salvianolic acid D (SaD), rosmarinic acid (RA) and salvianolic acid B (SaB). The pharmacokinetic parameters of the combination group or the Danhong injection alone group were calculated by statistical moment method, Cmax and the average of the area under the curve AUC0-t using 90% confidence interval of the bioequivalence and bioavailability degree module in DAS 3.2.8 statistic software. The results showed that Cmax of p-CA, SaD, RA and SaB were unqualified within 90% confidence intervals for bioequivalence statistics. And the results showed that AUC0-t of SaD, RA and SaB within 90% confidence intervals for bioequivalence statistics were unqualified. There were no significant difference in the tmax (P>0.05). The results of anticoagulation in vivo showed that the international normalized ratio (INR), prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) were significantly increased when combined with CFTX (P<0.05 or P<0.01). The results in antithrombotic effects revealed that the thromboxane B2 (TXB2) level in serum was significantly decreased (P<0.01) in the combination group compared with Danhong injection alone. However, there was no significant difference in antiplatelet effects. These results suggest that CFTX may enhance the anticoagulation and antithrombotic effects of DHI through altering pharmacokinetics and pharmacodynamics in SD rats.
