Martin B R
Drug Metab Dispos. 1982 Mar-Apr;10(2):189-93.
The disposition of 3H-phencyclidine (PCP), as well as total metabolites, was studied in mice up to 21 days after either iv or po administration. Thirty minutes after either iv or po administration the highest concentrations of 3H-PCP were found in stomach. The next highest levels were in fat (iv), liver (po), and intestines (po) and the lowest levels were found in brain and plasma (iv and po). Twenty-four hours later, the levels of 3H-PCP in all tissues were less than 2% of the concentrations after 30 min. After 3 days, the only detectable levels were in fat, and were less than 1% of the 30-min levels. Trace quantities of 3H-PCP were detected in fat at 7, 14, and 21 days. The disposition of total metabolites differed from that of 3H-PCP in that total metabolite levels were highest in stomach, liver, and intestines 30 min after administration of 3H-PCP by both routes. After 24 hr the concentration of total metabolites in all tissues far exceeded that of 3H-PCP. The highest concentration of metabolites remained in liver, stomach, and intestines for 24 hr, but after 3 days the levels in stomach and intestines fell considerably. Metabolite levels were sustained in lung and liver up to 14 days and in lung up to 21 days. Mice were also treated with seven daily gavages of 3H-PCP to determine the extent of 3H-PCP and metabolite accumulation. 3H-PCP was found only in fat 7, 14, and 21 days after the last treatment, but these levels were quite low. Metabolite levels in lung and liver at all time points were 5-10 times greater than those following acute treatment. 3H-PCP does not appear to be sequestered to an appreciable extent in any tissue in mice, whereas metabolites do accumulate in lung and liver for long periods of time.
在小鼠静脉注射或口服3H-苯环己哌啶(PCP)后长达21天的时间里,对其以及总代谢产物的处置情况进行了研究。静脉注射或口服给药30分钟后,在胃中发现3H-PCP的浓度最高。其次是脂肪(静脉注射)、肝脏(口服)和肠道(口服)中的浓度,而在脑和血浆(静脉注射和口服)中的浓度最低。24小时后,所有组织中3H-PCP的浓度低于给药30分钟后浓度的2%。3天后,唯一可检测到的浓度出现在脂肪中,且低于30分钟时浓度的1%。在第7、14和21天,在脂肪中检测到微量的3H-PCP。总代谢产物的处置情况与3H-PCP不同,即通过两种途径给予3H-PCP后30分钟,总代谢产物水平在胃、肝脏和肠道中最高。24小时后,所有组织中总代谢产物的浓度远远超过3H-PCP的浓度。代谢产物的最高浓度在肝脏、胃和肠道中持续24小时,但3天后胃和肠道中的水平大幅下降。肺和肝脏中的代谢产物水平可持续14天,在肺中可持续21天。还对小鼠进行了连续7天每天灌胃3H-PCP的处理,以确定3H-PCP和代谢产物的蓄积程度。在最后一次处理后的第7、14和21天,仅在脂肪中发现了3H-PCP,但这些水平相当低。在所有时间点,肺和肝脏中的代谢产物水平比急性处理后的水平高5至10倍。3H-PCP在小鼠的任何组织中似乎都不会大量被隔离,而代谢产物确实会在肺和肝脏中长期蓄积。