The distribution and metabolism of 14C-labelled tamoxifen in spayed female mice.

The distribution and metabolism of 14C-tamoxifen (a non-steroidal triaryl ethylene anti-oestrogen) have been investigated in ovarieectomized mice. The autoradiograms showed accumulation of radioactivity in the liver and the bile as an indication of an excretory pathway, but a rapid and high accumulation was also seen in the lung and the adrenals, organs normally not considered as target organs for tamoxifen. The liver and sebaceous glands could be detected on the autoradiograms up to fourteen days after a single intravenous dose. However, in most organs the amount of retained radioactivity was very low after 24 hours. By using the autoradiograms as a guideline a metabolic study was performed. High concentrations of unmetabolized tamoxifen was detected in the lung and the adrenals as well as in the pancreas. Relatively high amounts of a compound tentatively identified as 4-hydroxy-tamoxifen were present in the pancreas and the liver and there were also indications for the presence of N-desmethyl-tamoxifen in these tissues. These metabolites are considered to possess anti-oestrogenic activity.