Kindler J, Mödder G, Sieberth H G
Arzneimittelforschung. 1985;35(3):599-602.
In a macroautoradiographic study in pregnant and nonpregnant mice the distribution pattern of 14C-Endralazine (6-Benzoyl-3-hydrazino-5,6,7,8-tetrahydropyrido(4,3-c)-pyridazine- mesilate), a new direct vasodilator drug, was investigated, since earlier studies with minoxidil and hydralazine had shown apparent discrepancies between the relatively short elimination-half-life and the long pharmacological effect of the drugs. After a single oral administration of 5 mg/kg 14C-endralazine the initial high amounts of radioactivity in the gastro-intestinal tract, the kidneys and the liver continuously decreased in the course of the 2nd to the 8th hour after application. 24 h after administration the drug was nearly completely eliminated from these organs except the liver. A remarkably high and persistent affinity of 14C-radioactivity to the blood vessel walls was found even 48 h after application which could explain the long acting pharmacological response to the drug. Only low levels of radioactivity were registrated in the fetus of pregnant mice.
在一项针对怀孕和未怀孕小鼠的宏观放射自显影研究中,对一种新型直接血管扩张剂药物14C-恩屈嗪(6-苯甲酰基-3-肼基-5,6,7,8-四氢吡啶并(4,3-c)-哒嗪-甲磺酸盐)的分布模式进行了研究,因为早期使用米诺地尔和肼屈嗪的研究表明,这些药物相对较短的消除半衰期与较长的药理作用之间存在明显差异。单次口服5mg/kg的14C-恩屈嗪后,胃肠道、肾脏和肝脏中最初较高的放射性在给药后第2至8小时内持续下降。给药24小时后,除肝脏外,这些器官中的药物几乎完全消除。即使在给药48小时后,也发现14C放射性对血管壁具有非常高且持久的亲和力,这可以解释该药物的长效药理反应。在怀孕小鼠的胎儿中仅记录到低水平的放射性。