Tamoxifen administration and metabolism in nude mice and nude rats

We investigated the kinetics of tamoxifen (tam) in immunodeficient mice and rats after oral treatment and compared drug and metabolite profile in nude rat serum and tissues after oral and subcutaneous (s.c.) routes of administration. The serum levels were compared to those observed in man. After oral dosing in mice, tam and the potent metabolite 4-hydroxytamoxifen (4-hydroxytam), were detectable in liver and lung tissue, but not in serum. The levels of 4-hydroxytam in these tissues were significantly higher than those of tam, a profile opposite to that observed in rat and man. In rats and man, the 4-hydroxytam/tam serum concentration ratios were 0.16 and 0.02, respectively. Compared to oral route, the s.c. pellets yielded only trace amounts of the demethylated derivatives of tam in rats. Thus, the kinetics of tam observed in the present study suggest that the nude rat may represent a preferable animal model in studying the pharmacokinetics of tam and that, the oral route yielded higher serum and tissue levels of tam and metabolites than equivalent s.c. pellet implants.