Influence of Radix Salviae Miltiorrhizae on Methotrexate Pharmacokinetics in Rats / 广州中医药大学学报

ABSTRACT

Objective To compare the pharmacokinetics difference of methotrexate ( MTX) alone or MTX combined with the decoction of Radix Salviae Miltiorrhizae ( RSM) in rats, and to investigate the possible impact of RSM on the efficacy and pharmacokinetics of MTX after oral administration. Methods Sprague-Dawley rats were given MTX (7 mg/kg) alone or MTX together with RSM (3.085 g/kg) respectively. At different time points, blood was sampled from orbital venous plexus and then was precipitated by perchloric acid. The serum concentration of MTX was determined by using high performance liquid chromatography ( HPLC) method. Chromatographic separation was achieved on a reversed-phase Diamonsil C18 (2) column with the mobile phase of methanol-formic acid water solution (formic acid in volume fraction of 0.1%) in gradient elution. The column temperature was 27 ℃, flow rate was 1 mL/min, detection wavelength was 302 nm, and the injection volume was 10 μL. The results were analyzed by pharmacokinetic software DAS ( 2.1.1) by non-compartment model. Results The linearity of the calibration curve for MTX was good in the range of 0.097 6 ~ 12.5 mg/L, the detection limit was 0.097 6 mg/L and the recovery was in the range of 77.5% ~ 86.6%. Compared with MTX group, the peak-arriving time of MTX-RSM group was advanced, and the clearance of MTX was delayed. Area under concentration-time curve at 0-t (AUC(0-t)) was increased by 0.609 times, and AUC(0-∞) was increased by 0.786 times. Conclusion The decoction of RSM exerts an effect on promoting the absorption of MTX, delaying the clearance of MTX and enhancing the bioavailability of MTX in vivo.