The influence of Javanese turmeric (Curcuma xanthorrhiza) on the pharmacokinetics of warfarin in rats with single and multiple-dose studies

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 Blood samples were withdrawn daily at 4 h after administration of WF from the 1st to 11th day.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.