异汉防已甲素在大鼠体内的药代动力学及其组织分布

PHARMACOKINETICS AND DISTRIBUTION OF ISOTETRANDRINE IN RATS

本文报道用反相高效液相色谱法测定生物样品中异汉防己甲素的含量,其最低检出极限可达10 ng/ml。大鼠ⅳ异汉防已甲素的时量曲线属二室开放模型。给大鼠ⅳ本品12.5及25mg/kg后,药物自血浆的消除符合线性动力学,但ⅳ50mg/kg后为非线性动力学。组织分布以肺脏含量最高,血浆最低。大鼠ig异汉防己甲素100及250 mg/kg后,其血浆的时量曲线呈明显的双峰现象。其组织分布以肝脏含量最高,血浆最低。

A reversed-phase HPLC method for determination of isotetrandrine (ITD) in biological specimens was developed. The mobile phase composed of 0.2% (w/v) SDS, 47% acetonitrile and 53% distilled water(pH 2), at a flow rate of 1.5 ml/min with determination wavelength of 230nm. The drug concentration-time curves of ITD in rats after iv of 12.5,25 and 50 mg/kg were shown to fit a two-compartment open model with half_lives of 67.1±6.22 68.0±2.57 and 97.6±14.6 min, respectively. At doses of 12.5 and 25 mg/kg, the elimination of the drug from plasma was found to be in accord with linear kinetics, but when the dosage was 50 mg/kg, a non-linear kinetics was observed. Following ig ITD 100 and 250 mg/kg, the plasma concentration-time curves exhibited two marked peaks. Half-lives of elimination after ig doses was much longer than after iv administration, with mean values of 9.35±3.24 h(100 mg/kg) and 9.01±3.02h(250 mg/kg). Distribution of the drug in rats was extensive, highest level of the drug was found in the lung and lowest in plasma after iv administration. Following ig administration, highest level of the drug was found in the liver and lowest in plasma.