Leeson G A, Chan K Y, Knapp W C, Biedenbach S A, Wright G J, Okerholm R A
Arzneimittelforschung. 1982;32(9a):1173-8.
Alpha-[4-(1,1-Dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1- piperidinebutanol (terfenadine, RMI 9918, Triludan, Teldane, resp.), a clinically effective antihistamine, with little or no central nervous system effects, was investigated in order to understand its metabolic disposition. These 14C-terfenadine studies were performed in laboratory animals, principally the rat, and also in beagle dog and monkey (Macaca mulatta). In all three species the fecal pathway of excretion was predominant with nearly all the elimination occurring within 24 h of administration. The data suggest that biliary excretion plays a prominent role. Tissue distribution studies indicated that the liver and lung, relative to other tissues, exhibited the highest concentrations of 14C-terfenadine equivalents. However, brain had low amounts of 14C-terfenadine which was in general agreement with the whole-body autoradiographic studies which did not show radioactivity in brain or spinal cord. The evidence suggests that terfenadine was metabolized rapidly with no terfenadine in urine or bile and small amounts in feces. Tissue concentrations of terfenadine were in the low nanogram range and peaked at 0.5-1.0 h with lung exhibiting the greatest and the brain sub-quantifiable amounts. The ratios of 14C-terfenadine eq/terfenadine were high and greatest in the liver and kidney. These studies demonstrated that terfenadine was readily absorbed and eliminated, virtually had undergone complete biotransformation and exhibited very low tissue concentrations per se.
α-[4-(1,1-二甲基乙基)苯基]-4-(羟基二苯甲基)-1-哌啶丁醇（特非那定，商品名分别为RMI 9918、Triludan、Teldane）是一种临床有效的抗组胺药，对中枢神经系统几乎没有影响。为了解其代谢情况，我们对其进行了研究。这些用14C标记特非那定的研究在实验动物身上进行，主要是大鼠，也包括比格犬和恒河猴（猕猴）。在这三种动物中，粪便排泄途径占主导地位，几乎所有的药物在给药后24小时内排出。数据表明胆汁排泄起了重要作用。组织分布研究表明，相对于其他组织，肝脏和肺中14C-特非那定等效物的浓度最高。然而，脑中14C-特非那定的含量很低，这与全身放射自显影研究结果基本一致，该研究未显示脑或脊髓中有放射性。证据表明特非那定代谢迅速，尿液或胆汁中没有特非那定，粪便中有少量。特非那定的组织浓度处于低纳克范围，在0.5 - 1.0小时达到峰值，肺中的浓度最高，而脑中的含量低于可检测量。肝脏和肾脏中14C-特非那定等效物与特非那定的比率很高且最大。这些研究表明特非那定易于吸收和消除，实际上已完全进行生物转化，其本身在组织中的浓度非常低。
