Serum kinetics of the anti-cancer agent 4-hydroxyandrostenedione in the rat.

A previously described radioimmunoassay (RIA) method for the measurement of 4-hydroxyandrostenedione (4-OHA) was used to investigate the serum drug levels attained after a single oral dose in male and female rats. Marked variability of serum drug concentrations and their time course were evident in male animals at all dose levels. In the female rat, in contrast, serum 4-OHA showed fewer individual differences, rose more rapidly and was sustained at substantially higher concentrations. In all animals, 4-OHA appeared in the serum within 0.5 h following the oral dose and persisted for at least 48 h. Doubling the dose from 8 mg/kg produced a disproportionately large elevation in serum drug levels, but a further increase to 32 mg/kg did not further increase serum levels.