Ings R M
Arch Int Pharmacodyn Ther. 1979 Dec;242(2):180-95.
The disposition of radioactivity from 14C-nomifensine has been compared in pregnant and non-pregnant female rats by examining plasma profiles, the qualitative tissue distribution (whole body autoradiography) and the quantitative tissue distribution of radioactivity. The clearance of radioactivity of 14C-nomifensine from the plasma of pregnant and non-pregnant rats was similar and was complex with secondary peaks and plateaux after both oral and intravenous dosing. Maximum plasma levels (mean +/- S.D., 0.20 +/- 0.05 and 0.22 +/- 0.02 microgram equivalents nomifensine/ml plasma for pregnant and non-pregnant rats respectively) occurred at 30 to 45 min after oral dosing. The biological half-life of radioactivity in plasma was between 4 and 5 hr for both routes of administration, although there was an additional rapid initial phase (t 1/2 approx. 20 min) after intravenous dosing. Whole body autoradiography also showed a very similar tissue distribution pattern of radioactivity between pregnant and non-pregnant rats with extensive distribution from blood into tissue. Only traces of radioactivity from 14C-nomifensine were seen to cross the placenta into the foetuses of 15-day pregnant rats and these rapidly cleared with time. Slightly higher amounts were seen to cross the foetuses of 18-day pregnant rats and radioactivity was seen in the foetal brain, heart, liver and lung. Quantitative tissue distribution studies confirmed these qualitative findings. The biological half-life of radioactivity in both adult and foetal tissues was approximately 5 hr, except for adult livers where a longer half-life of radioactivity of approximately 10 hr was found.
通过检测血浆曲线、放射性的定性组织分布（全身放射自显影）和放射性的定量组织分布，比较了怀孕和未怀孕雌性大鼠体内(^{14}C -)诺米芬辛的放射性分布情况。怀孕和未怀孕大鼠血浆中(^{14}C -)诺米芬辛的放射性清除情况相似，口服和静脉给药后均出现复杂的情况，伴有继发性峰和平台期。口服给药后，怀孕和未怀孕大鼠的最大血浆水平（平均值±标准差，分别为(0.20±0.05)和(0.22±0.02)微克当量诺米芬辛/毫升血浆）在(30)至(45)分钟出现。两种给药途径下，血浆中放射性的生物半衰期均在(4)至(5)小时之间，不过静脉给药后有一个额外的快速初始阶段（(t_{1/2})约为(20)分钟）。全身放射自显影还显示，怀孕和未怀孕大鼠之间放射性的组织分布模式非常相似，放射性从血液广泛分布到组织中。在(15)天孕期大鼠的胎儿中，仅见微量(^{14}C -)诺米芬辛的放射性穿过胎盘，且这些放射性随时间迅速清除。在(18)天孕期大鼠的胎儿中可见稍多的放射性穿过，且在胎儿的脑、心、肝和肺中可见放射性。定量组织分布研究证实了这些定性结果。除成年肝脏中放射性半衰期约为(io)小时较长外，成年和胎儿组织中放射性的生物半衰期约为(5)小时。
