yup, you're right. possibly letro, too:
: Br J Cancer. 2001 Aug 3;85(3):317-24. Links
Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the 'Arimidex and tamoxifen alone or in combination' (ATAC) trial.Dowsett M, Cuzick J, Howell A, Jackson I; ATAC Trialists' Group.
CRC and UCL Cancer Trials Centre, University College London, Stephenson House, 158-160 N Gower Street, London, NW1 2ND, UK.
The ATAC trial evaluates in a randomized, double-blind design, Arimidextrade mark (anastrozole) alone or in combination with tamoxifen, relative to tamoxifen alone as 5-year adjuvant treatment in postmenopausal women with early breast cancer. Patients included in the pharmacokinetic (PK) sub-protocol had been in ATAC for > or =3 months, taking their medication in the morning and were 100% compliant for the preceding 14 days. Blood samples were collected 24 +/- 4 h after last dose. Trough (C(min)) plasma concentrations of anastrozole, tamoxifen and desmethyltamoxifen (DMT) were measured by validated methods. The PK results were based on a total of 347 patients (131 anastrozole (1 mg o.d.), 111 tamoxifen (20 mg o.d.), 105 anastrozole and tamoxifen (1 and 20 mg o.d. respectively)). The geometric mean steady-state trough plasma concentrations of tamoxifen and DMT were statistically equivalent in patients receiving tamoxifen alone or in combination with anastrozole: geometric mean tamoxifen = 94.8 ng ml(-1)and 95.3 ng ml(-1)in tamoxifen alone and combination groups, respectively; geometric mean DMT = 265.1 and 277.6 ng ml(-1)in the tamoxifen and anastrozole and tamoxifen groups, respectively. The geometric mean anastrozole levels were 27% lower (90% Cl 20-33%< 0.001) in the presence of tamoxifen than with anastrozole alone. Baseline plasma oestradiol levels were not obtained in the PK sub-protocol, however, such information was available from a similar ATAC sub-protocol, which evaluated bone mineral density. Mean oestradiol levels were 21.3, 19.3, and 21.6 pmol l(-1)prior to treatment and 3.7, 20.9 and 3.6 pmol l(-1)after 3 months in the anastrozole, tamoxifen, and combination groups, respectively (n = 167). On-treatment values were below the detection limit (3 pmol l(-1)) in 43.6 and 38.5% of the anastrozole alone and anastrozole in combination with tamoxifen groups, respectively. As a result of (a) the lack of effect of anastrozole on tamoxifen and DMT levels and (b) the observed fall in blood anastrozole levels having no significant effect on oestradiol suppression by anastrozole, we conclude that the observed reduction in anastrozole levels by tamoxifen is unlikely to be of clinical significance when anastrozole and tamoxifen are administered together. Copyright 2001 Cancer Research Campaign.
it has a more significant impact on letrozole metabolism
1: Biopharm Drug Dispos. 2006 Aug 15;27(7):335-344 [Epub ahead of print] Links
The effect of tamoxifen on the pharmacokinetics of letrozole in female rats.Tao X, Brodie AM, Nnane IP.
Temple University School of Pharmacy, Philadelphia, PA, USA.
The effects of single doses of tamoxifen (TAM; 0.5-5 mg/kg, i.v.) and chronic pretreatment with TAM (0.1-5.0 mg/kg/day, i.p. for 7 consecutive days) on letrozole (0.5 mg/kg, i.v.) pharmacokinetics were evaluated in female Sprague-Dawley rats. The plasma concentration-time profiles of letrozole (0.1-2.0 mg/kg) after single i.v. doses were analysed by the non-compartment model with terminal half-lives (t(1/2,lambdaz)) ranging from 34.3 to 37.5 h. The volume of distribution at the terminal phases (V(d(lambdaz))) ranged from 1.9 to 2.1 l/kg and clearance (CL) varied from 0.036 to 0.042 l/(h.kg). After co-administration of TAM and letrozole intravenously, the t(1/2), V(d(lambdaz)) and CL of letrozole were not significantly altered. Chronic pretreatment with TAM significantly decreased the t(1/2) of letrozole by about 33%, and increased its clearance by an average of 40%. However, TAM pretreatment did not significantly affect the V(d((lambdaz)) of letrozole in female rats. Co-administration of letrozole and TAM orally increased the absorption half-life of letrozole threefold although the absolute bioavailability remained unchanged. These observations suggest that single oral doses of TAM delay the absorption of letrozole while chronic pretreatment with TAM accelerates the elimination of letrozole, probably due to induction of cytochrome P450 enzymes in rats. Copyright (c) 2006 John Wiley & Sons, Ltd.