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Xenobiotica
the fate of foreign compounds in biological systems
Volume 50, 2020 - Issue 6
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Animal Pharmacokinetics and Metabolism

Effects of sulfotanshinone sodium injection on the pharmacokinetics and pharmacodynamics of warfarin in rats in vivo

, , , , , , , & show all
Pages 705-712 | Received 29 Jul 2019, Accepted 13 Oct 2019, Published online: 28 Oct 2019
 

Abstract

  1. This study was to explore the effects of sulfotanshinone sodium injection (SSI) on the pharmacokinetics and pharmacodynamics of warfarin in rats.

  2. The studies of single dose and multiple dose of warfarin were designed to assess the interaction between warfarin and SSI. Rats were divided into different groups randomly and administered with warfarin in the absence or presence of SSI. Prothrombin time (PT) and activated partial thromboplastin time (APTT) values were detected by blood coagulation analyzer, and international normalized ratio (INR) values were calculated. Plasma concentrations of warfarin enantiomers were determined by UPLC–MS/MS method, pharmacokinetic parameters were calculated.

  3. The single-dose study demonstrated that the repeated doses of SSI alone had no effect on PT, APTT and INR values, but had a significant effect on PT and INR values produced by a single dose of warfarin, APTT values were unaffected. The Cmax, AUC of R-warfarin and S-warfarin were reduced, t1/2 were shortened. The multiple-dose study showed that PT, APTT, INR values, and the Cmax and AUC of R-warfarin and S-warfarin decreased significantly after administration of SSI.

  4. The finding implied that SSI could accelerate warfarin metabolism and weaken its anticoagulation. However, human SSI–warfarin interaction studies need to be conducted to confirm this finding.

Disclosure statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (81173659).

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