【摘要】 为全面了解萘哌地尔（Ｎａｆ）在大鼠体内的代谢过程，用反相ＨＰＬＣＵＶ法，给大鼠ｉｇ１０，２０，３０ｍｇ·ｋｇ－１Ｎａｆ后，测定在不同时间各组织和体液中Ｎａｆ的含量。结果表明，Ｎａｆ在大鼠体内药代动力学为二室模型，Ｔ１／２α为０４７～１０１ｈ，Ｔ１／２β为４７８～７０８ｈ，达峰时间Ｔ（ｐｅａｋ）为０４２～０９０ｈ，Ｃｍａｘ，ＡＵＣ随剂量升高而增大。给药后１５ｍｉｎ，肠壁组织浓度最高，其次为肝、肺；２ｈ以后，除睾丸、卵巢和子宫外，其余组织药物浓度逐渐降低。尿、粪及胆汁中原形药总排出量不足给药量的１％，提示Ｎａｆ在大鼠体内有首过效应及代谢物生成。在１００～５００ｍｇ·ｍｌ－１浓度范围内，Ｎａｆ血浆蛋白结合率为８２％～９７％。更多还原

【Abstract】 Naftopidil(Naf), a novel antihypertensive drug, was determined by HPLCUV method. The plasma concentration and pharmacokinetics of naftopidil have been investigated in rats after single oral doses of 10, 20 and 30 mg·kg-1. The drug was found to conform to a twocompartment model. Tp was in the range of 042 h to 090 h. T1/2β was 708 h after the 10 mg·kg-1 dose, 478 h after the 20 mg·kg-1 dose and 583 h after the 30 mg·kg-1 dose. The Cmax, AUC and CL/F appeared to be dose dependent at the doses not higher than 20 mg·kg-1. Naf was found in many tissues after a single oral dose of 20 mg·kg-1. The top level tissues were intestine, liver and lung at 15 minutes after administration, while the uteroovarian tissue was the highest at 6 h. Naf can be extensively metabolized since the total excretion of the parent compound in urine and faeces was less than 1% of the dose. From 82% to 97% of Naf in plasma was shown to be bound to protein.更多还原