SERUM AND URINE LEVELS OF TAMOXIFEN AND ITS METABOLITES IN PATIENTS WITH ADVANCED BREAST-CANCER AFTER A LOADING DOSE AND AT STEADY-STATE LEVELS

Purpose: To compare serum and urine levels of tamoxifen and metabolite s after a loading dose and at the steady state. Methods: A loading dos e of 160 mg of tamoxifen was given to 14 patients with advanced breast cancer. Thereafter a regular daily dose of 30 mg of tamoxifen was giv en. Serum and urine levels of tamoxifen and metabolites were measured by high-performance liquid chromatography and compared with levels det ermined in 31 patients with advanced breast cancer at the steady state at a daily dose of 30 mg of tamoxifen. Results: Serum and urine level s (24-h values) of tamoxifen and metabolites were lower (P < 0.05) aft er a loading dose than at the steady state. The difference was most pr onounced for the metabolites, whereas the tamoxifen loading-dose level was near the steady state. Conclusion: Tamoxifen steady state can be reached in 1-2 days by the administration of a loading dose of 160 mg of tamoxifen for 2 days. Tamoxifen metabolite steady-state levels are reached regularly after 4 or more weeks during application of a loadin g dose. Very little tamoxifen or metabolites are excreted into the uri ne.