Effects of Xiangdan Injection on pharmacokinetics and pharmacodynamics of warfarin in rats in vivo

JIANG Mei-ting1 ZHANG Wen-long1 SUN Zhi-dan1 ZHOU Yang-xu1 CHEN Jia-yu1 LIU Gao-feng1

(1.Key Laboratory of University in Heilongjiang Province, Department of Pharmacy, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China 150086)

【Abstract】This study aimed at exploring the effect of Xiangdan Injection on anticoagulation of warfarin in rats in vivo. Rats were randomly assigned into different groups and then administered. Subsequently, the blood samples were collected at a set series of time points for the measurement of prothrombin time (PT) and activated partial thromboplastin time (APTT) values, and the international normalized ratio (INR) was calculated. The plasma concentrations of warfarin enantiomers were determined by UPLC-MS/MS technology, and pharmacokinetic parameters were calculated by DAS 2.0 software. Statistical analysis was performed to compare differences between the groups. Single-dose study of warfarin showed that Xiangdan Injection alone had no effects on PT, APTT or INR. When Xiangdan Injection was co-administered with warfarin, PT and INR values increased (P < 0.01), while APTT was unaffected; after co-administration of the two drugs, Cmax, AUC0-t, and AUC0-∞ of S-warfarin increased (P < 0.01), and t1/2 prolonged (P < 0.01), while the pharmacokinetic parameters of R-warfarin changed insignificantly. Steady-state study of warfarin showed that after co-administration of the two drugs, the PT and INR values increased (P < 0.05), and the plasma concentration of S-warfarin increased (P < 0.01), while the plasma concentration of R-warfarin changed insignificantly. The results have suggested that Xiangdan Injection itself has no effect on coagulation index while can enhance the anticoagulation of warfarin by delaying the metabolism of S-warfarin.

【Keywords】 Xiangdan Injection; warfarin; anticoagulation; drug interactions; pharmacodynamics; pharmacokinetics;

【DOI】

【Funds】 National Natural Science Foundation of China (81173659)

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This Article

ISSN:1001-5302

CN: 11-2272/R

Vol 45, No. 19, Pages 4740-4745

October 2020

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Article Outline

Abstract

  • 1 Materials
  • 2 Methods
  • 3 Results
  • 4 Discussion
  • References