The metabolism of 2,4-dibromo-17α-ethynyl[6,7-3H]oestradiol in the rat

1. The metabolism of 2,4-dibromoethynyloestradiol (2,4-DBEE2) in the rat was studied in order to determine the influence of ring-A substituents on the phase I biotransformations of oestrogens. 2. 2,4-Dibromo-17α-ethynyl[6,7-3H]oestradiol was synthesized by the one-stage bromination of 17α-ethynyl[6,7-3H]oestradiol (EE2) with N-bromoacetamide, and administered (30 μg/kg, i.v.) to anaesthetized male and female rats. 3. A single metabolite, identified as a glucuronide of 2,4-DBEE2, was rapidly and extensively eliminated in bile by male rats (83% of the dose over 6 h). Females excreted additional minor conjugated metabolites. Neither unchanged 2,4-DBEE2 nor EE2 was detected in bile. 4. The hepatic residues after 6 h (percentage of dose) were 2.7% and 3.4% in male and female rats, respectively, whilst