Tamoxifen metabolic patterns within a glioma patient population treated with high‐dose tamoxifen

摘要: AIMS The study was designed to evaluate tamoxifen metabolic profiles in 25 patients (13 M, 12 F) suffering from recurrent high-grade cerebral astrocytomas who were treated with high oral doses of (120 mg/m2 twice daily). METHODS Tamoxifen administered for at least 8 weeks; after 4 weeks blood samples collected 7 h post dose. and metabolites analysed by h.p.l.c. RESULTS Steady-state plasma concentrations (mean microM +/- s.d.) determined (2.94 3.44), N-desmethyltamoxifen (4.37 2.13), N-desdimethyltamoxifen (1.49 0.54), 4-hydroxytamoxifen (0.13 0.05) primary alcohol (1.07 0.46). Male female had comparable profiles, both qualitatively quantitatively. mean higher dexamethasone-treated than untreated patients: 3.94 4.35 (95% C.I.: 1.43-6.46) vs 1.67 0.84 1.11-2.24), without; while phenytoin-treated lower concentrations: 1.85 0.87 1.37-2.34) 4.58 5.05 0.97-8.19), without. differences approached but did not reach statistical significance (P = 0.065 0.078 respectively). CONCLUSIONS There marked interpatient variability. observed effect dexamethasone on is consistent the involvement CYP3A metabolism.