| Abstract: | 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. |
