https://orcid.org/0000-0002-3321-2179
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Abstract
Context
Co-administration between warfarin (WF) and Curcuma xanthorrhiza Roxb. (Zingiberaceae) (CX) is found in Indonesian patients and need to be evaluated.
Objective
This study assesses the effect of concomitant administration of CX extract on the pharmacokinetics of WF in rats.
Materials and methods
Wistar rats were divided into 4 groups (n = 6) and administered with 2% Pulvis Gummi Arabicum (PGA, control), fluconazole (FZ, 6 mg/kg), CX-1 (6 mg/kg) or CX-2 (18 mg/kg BW) for 7 days. For the single-dose study, at the 8th day, WF (1 mg/kg) was administered to all groups and blood samples were taken from 0.25 to 72 h. For the multiple-dose study, daily dose of WF was administered to all groups of rats and at the 7th to 9th day, the rats were treated with PGA, CX-1, CX-2 and FZ. Blood samples were withdrawn daily at 4 h after administration of WF from the 1st to 11th day.
Results
The area under the curve (AUC) of R- and S-WF in the CX-2 group was a significantly higher value compared to the control (77.54 vs. 35.27 mg.h/L for R-WF and 316.26 vs. 40.16 mg.h/L for S-WF; p < 0.05; Kruskal-Wallis method). The CX-2 administration also caused the increasing in the concentration level of R-WF (16%) and S-WF (27%) from the 7th to 9th day of administration.
Discussion and Conclusions
The CX administration in a higher dose caused alteration on WF pharmacokinetics suggesting the need for clinical evaluation of the interaction between CX and WF.
Acknowledgments
The authors are grateful to the laboratory research assistant at the Department of Clinical Pharmacology/Department of Pharmacy, Gunma University of Graduate School of Medicine for technical support including the material and equipment used.
Disclosure statement
No potential conflict of interest was reported by the author(s).