Letrozole pharmacokinetics

In terms of pharmacokinetics, letrozole is well absorbed following 2.5-mg oral administration in healthy postmenopausal women. The maximum plasma concentration of... 

Dowsett M, Pfister C, Johnston SR, Miles DW, Houston SJ, Verbeek JA, Gundacker H, Sioufi A, Smith IE. Impact of tamoxifen on the pharmacokinetics and endocrine effects of the aromatase inhibitor letrozole in postmenopausal women with breast cancer. Clin Cancer Res 1999 5(9) 2338-43. 

The manufacturers report that letrozole had no clinically relevant effect on the pharmacokinetics of warfarin. ... 

The pharmacokinetics of a single 2.S-mg dose of letrozole were unchanged by cimetidine 400 mg every 12 hours in 17 healthy subjects. ... 

In 6 menopausal women with breast cancer aminoglutethimide 250 mg four times daily for 6 weeks markedly reduced the serum levels of tamoxifen 20 to 80 mg daily and most of its metabolites. The clearance of the tamoxifen was inereased by 3.2-fold and the tamoxifen AUC was re-dueed by 73% (range 56 to 80%). Conversely, the concurrent use of anastrozole 1 mg daily for 28 days did not affect the pharmacokinetics of tamoxifen in a double-blind, placebo-controlled study in 34 women with breast eaneer who had been taking tamoxifen 20 mg daily for at least 10 weeks. Similarly, letrozole 2.5 mg daily had no effeet on the pharma-eokineties of tamoxifen in 18 women taking tamoxifen 20 mg daily. Further, a study in 32 women clinically disease-free following primary treatment for breast eaneer and who had been taking tamoxifen 20 mg daily for at least 4 months found that exemestane 25 mg daily for 8 weeks... 

Tamoxifen 20 to 80 mg daily did not alter the pharmacokineties of aminoglutethimide 250 mg four times daily. In a pilot study, 18 postmenopausal women with breast cancer were gi ven exemestane 25 mg daily for 14 days, then exemestane and tamoxifen 20 mg daily for 4 weeks. Tamoxifen did not affect the pharmacokinetics (plasma levels) or pharmacodynamics (estrone, estrone sulfate and estradiol suppression) of exemestane and the eombination was well-tolerated. In 12 women letrozole levels were reduced by 38% (range 0 to 70%) 6 weeks after tamoxifen 20 mg daily was added to letrozole 2.5 mg daily. This redue-tion persisted after 4 to 8 months however, the estradiol suppressant effeets of letrozole did not appear to be affected. Similarly, although the estradiol suppressant effects of anastrozole 1 mg daily did not appear to be affeeted by tamoxifen 20 mg daily in two studies, in one of these studies, anastrozole levels were deereased by 27% by tamoxifen. ... 

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