没食子酸在大鼠体内的药物动力学及生物利用度

Pharmacokinetics and absolute bioavailability of gallic acid in rat plasma

目的建立大鼠血浆中没食子酸的高效液相测定方法；研究大鼠灌胃与静脉给药后没食子酸的药物动力学过程及生物利用度。方法分别灌胃和静脉给予大鼠没食子酸，不同时间点采血。样品经甲醇沉淀蛋白后。采用Phenomenex C18（250mm×4．6mm，4μm）色谱柱，甲醇-体积分数为0．5％的冰醋酸水溶液（体积比为7：93）为流动相，流速为1．0mL·min^-1，检测波长为272nm，以对乙酰氨基酚为内标测定血浆中没食子酸的浓度。应用DAS2．0软件计算药物动力学参数。结果大鼠灌胃给药后t1／2。为46．57min，t1／2β为56．54min，tmax为66．00min，ρmax为3．96mg·L^-1，AuC0～t为396．5mg·min·L^-1；静脉给药后t1／2α为9．90min，t1／2β为78．88min，AUC0～t为461．9mg·min·L^-1。结论大鼠灌胃和静脉给予没食子酸后，其药-时过程均符合二室模型，绝对生物利用度为42．9％。

Objective To develop a method for the quantitative determination of gallic acid in rat plasma by high performance liquid chromatography （HPLC）, and study the pharmacokinetics and absolute bioavailability in rats. Methods Acetaminophen was selected as internal standard, and the plasma samples were pretreated by protein precipitation with methanol. Phenomenex C18 was used with the mobile phase of methanol and water contained 0.5 % glacial acetic acid （ V ： V = 7 ： 93） at a flow rate of 1.0 mL· min^- 1, and detection wavelength was set at UV 272 nm. Results After ig of gallic acid, the values of t1/2a, t1/2β, tmax, ρmax and AUC0- t were 46.57 min, 56.54 min, 66.00 min, 3.96 mg· L^- 1 and 396.5 mg· min·L^- 1, respectively; As for iv, t 1/2α, t 1/2β and AUC0- t, the values were 9.90 min, 78.88 min and 461.9 mg· min· L^- 1, respectively. Conclusions The concentration-time curves of gallic acid in rats after ig and iv administration shows that they both fit two-compartment model. Absolute bioavailability of gallic acid is 42.9 %.