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

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