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【目的】比较甲氨蝶呤(MTX)单用与联用丹参时大鼠体内药物动力学参数,探讨丹参对甲氨蝶呤药物动力学以及药效可能的影响。【方法】选用SD大鼠分别灌胃MTX(剂量为7 mg/kg)或MTX加丹参水煎剂(剂量为3.085 g/kg),于不同时间点眼眶静脉丛采血,采用高氯酸沉淀蛋白法处理血样,高效液相色谱法分析:Diamonsil C18(2)色谱柱;甲醇—体积分数0.1%甲酸水梯度洗脱;流速1 mL/min;柱温27℃;检测波长302 nm;进样量10μL。采用非隔室模型估算药物动力学参数。【结果】MTX在0.097 6~12.5 mg/L线性关系良好(r=0.998 5);定量下限0.097 6 mg/L;提取回收率77.5%~86.6%。与MTX组比较,联合用药组MTX达峰时间提前,清除延迟。其中药—时曲线下面积(0-t)[AUC(0-t)]增加0.609倍,药—时曲线下面积(0-∞)[AUC(0-∞)]增加0.786倍。【结论】丹参水煎液能够促进MTX吸收,延缓其消除,提高其生物利用度。
【Objective】 To compare the pharmacokinetic parameters of methotrexate (MTX) alone and in combination with Salvia miltiorrhiza in rats, and to explore the effect of Salvia miltiorrhiza on the pharmacokinetics and pharmacodynamics of methotrexate. 【Methods】 Sprague-Dawley rats received MTX (7 mg / kg) or MTX plus salvia miltiorrhiza decoction (3.085 g / kg) at different time points respectively. The rats were perfused with perchloric acid HPLC method: Diamonsil C18 (2) column; gradient elution with methanol-0.1% formic acid in water; flow rate 1 mL / min; column temperature 27 ℃; detection wavelength 302 nm; 10μL. Pharmacokinetic parameters were estimated using a non-compartmental model. 【Result】 MTX showed good linearity (r = 0.998 5) at 0.097 6 ~ 12.5 mg / L; the lower limit of quantitation was 0.097 6 mg / L; the recovery was 77.5% ~ 86.6%. Compared with the MTX group, the combination group MTX peak time ahead of schedule, clear delay. The area under the drug-time curve (0-t) [AUC (0-t)] increased by 0.609-fold and the area under the drug-time curve (0 -∞) [AUC (0-∞)] increased by 0.786-fold. 【Conclusion】 Radix Salviae Miltiorrhizae decoction can promote MTX absorption, delay its elimination and improve its bioavailability.