Summary
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1.
Imipramine labelled with carbon-14 in the 10, 11 position was injected in tracer dose into rats receiving 5–20 mg/kg orally, and the radioactivity recovered completely in urine and faeces collected over 6 days. Excretion was rapid, mostly in the first 24 or 48 hours, and from one-quarter to two-thirds of the administered dose was found in the faeces.
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2.
Radioactive imipramine was taken orally in tracer amount by depressed female patients under treatment with 150–300mg. imipramine daily. The radioactivity was also recovered to a large extent in 6 days. Excretion was rapid, an average of 36.6%, of the dose appearing in the first 24 hour urine specimen, and 65% in the urine by 72 hours. Up to 22% of the dose was recovered from the faeces.
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3.
The same individual, rat or human, usually but not always gave a similar excretion pattern on re-test. Individuals differed widely among themselves, however, in the way they excreted the radioactive dose within the 6 day period. These variations did not appear to depend on sex, on schedule of imipramine treatment, or on urinary pH. In man, but not in rat, the quantity of faeces may have influenced faecal excretion of the drug and its metabolites.
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4.
The implications of rapid excretion for the treatment of drug overdosage, and for the biochemical nature of the therapeutic action of imipramine, are briefly discussed.
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Crammer, J.L., Scott, B., Woods, H. et al. Metabolism of 14C-Imipramine. Psychopharmacologia 12, 263–277 (1968). https://doi.org/10.1007/BF00401406
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DOI: https://doi.org/10.1007/BF00401406