Abstract
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.
Keywords: tamoxifen, metabolism, males, females, blood
Full Text
The Full Text of this article is available as a PDF (254.4 KB).