Lu K, Loo T L
Cancer Res. 1980 May;40(5):1427-30.
1,4-Bis (2-[(2-hydroxyethyl)amino]ethylamino)-9,10-anthracenedione (NSC 287513) (HAQ) may be selected for clinical trial based on its activity against a number of transplantable rodent tumors. Using a high-pressure liquid chromatograph assay, we have studied the pharmacological fate of HAQ in beagles. After i.v. administration of HAQ at 15 mg/kg (300 mg/sq m), the initial plasma t1/2 of the agent was 9.4 min, and the terminal t1/2 was 115.2 min. A maximal plasma concentration of 24.9 mg of HAQ per liter was attained. A high plasma clearance of 23.5 ml/kg/min was observed in these animals. The extrapolated apparent volume of distribution was 693.7 ml/kg, comparable to that of antipyrine in the dog. In 5 hr, 24.0% of the administered HAQ has been excreted in the urine unchanged, and a trace of a metabolite was detected, amounting to less than 2% of the UV-absorbing (254 nm) materials. However, hepatobiliary excretion constituted the primary route of drug elimination since 39.5% of the dose was found in the bile during the same period. An extraction procedure has been developed to quantify HAQ in tissue homogenates with 75 to 80% recovery. At autopsy, 5 hr after dosing, drug distribution in terms of percentage of the dose administered is as follows: liver, 7%; kidneys, 3.5%; pancreas, 3.1%; small intestine, 1.5%; stomach, 1.3%; spleen, 0.7%; lungs, 0.5%; heart, 0.4%; large intestine, 0.4%; and brain, 0.2%.
1,4-双（2-[(2-羟乙基)氨基]乙基氨基）-9,10-蒽二酮（NSC 287513）（HAQ）因其对多种可移植啮齿动物肿瘤的活性，可能被选用于临床试验。使用高压液相色谱分析法，我们研究了HAQ在比格犬体内的药理转归。静脉注射15 mg/kg（300 mg/平方米）的HAQ后，该药物的初始血浆半衰期为9.4分钟，终末半衰期为115.2分钟。血浆最大浓度达到每升24.9 mg的HAQ。在这些动物中观察到血浆清除率高达23.5 ml/kg/分钟。推算的表观分布容积为693.7 ml/kg，与犬体内安替比林的表观分布容积相当。在5小时内，给药的HAQ中有24.0%以原形经尿液排出，并且检测到微量代谢物，其含量不到紫外线吸收（254 nm）物质的2%。然而，肝胆排泄是药物消除的主要途径，因为在同一时期，39.5%的剂量在胆汁中被发现。已开发出一种提取程序，用于定量组织匀浆中的HAQ，回收率为75%至80%。给药5小时后尸检时，按给药剂量的百分比计算的药物分布如下：肝脏7%；肾脏3.5%；胰腺3.1%；小肠1.5%；胃1.3%；脾脏0.7%；肺0.5%；心脏0.4%；大肠0.4%；脑0.2%。
