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Tamoxifen metabolic patterns within a glioma patient population treated with high‐dose tamoxifen
Author(s) -
Ducharme Julie,
Fried Karen,
Shenouda George,
LeylandJones Brian,
Wainer Irving W.
Publication year - 1997
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1997.05029.x
Subject(s) - tamoxifen , medicine , cyp3a , phenytoin , endocrinology , population , statistical significance , dexamethasone , antiestrogen , breast cancer , pharmacokinetics , metabolism , gastroenterology , cancer , epilepsy , cytochrome p450 , environmental health , psychiatry
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/m 2 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.