Anastrozole pharmacokinetics

Zeneca. Effect of cimetidine on anastrozole pharmacokinetics. Data on file, 1995. 

Anastrozole is a selective nonsteroidal aromatase inhibitor that lowers estrogen levels. The pharmacokinetics of anastrozole demonstrate good absorption, with hepatic metabolism the primary route of elimination and only 10% excreted unchanged by the kidney. The elimination half-life is approximately 50 hours. Anastrozole is used for the adjuvant treatment of postmenopausal women with hormone-positive breast cancer and in breast cancer patients who have had disease progression following tamoxifen. Side effects include hot flashes, arthralgias, osteoporosis/bone fractures, and thrombophlebitis. 

In 34 post-menopausal women with early breast cancer anastrozole 1 mg/day for 28 days had no effect on the pharmacokinetics of tamoxifen 20 mg/day (38). 

Dowsett M, Tobias JS, Howell A, Blackman GM, Welch H, King N, Ponzone R, von Euler M, Baum M. The effect of anastrozole on the pharmacokinetics of tamoxifen in postmenopausal women with early breast cancer. Br J Cancer 1999 79(2) 311-5. 

The ATAC Trialists Group, Pharmacokinetics of Anastrozole and Tamoxifen Alone, and in Combination, During Adjuvant Endocrine Therapy for Early Breast Cancer in Postmenopausal Women A Suh-Protocol of the Arimidex and Tamoxifen Alone or in Combination (ATAC) Trial, British Journal of Cancer 85 (2001) 317-324-... 

A randomised, double-blind, placebo-controlled, crossover study in 16 healthy men found that anastrozole (7 mg loading dose followed by 1 mg daily for a further 10 days) had no effect on the pharmacokinetics or pharmacodynamics of a single dose of warfarin given on day 3. 

In a pharmacokinetic study, 10 elderly women with breast cancer were given anastrozole 1 mg daily for 10 weeks and 5 of them who also had hypertension were additionally given quinapril, after week 4, for 28 days. Quinapril did not affect plasma anastrozole levels and dose modification is not required during concurrent use. A clinical study with cimetidine has shown that it does not affect the pharmacokinetics of anastrozole, which suggests that anastrozole is unlikely to be affeeted by other drugs that inhibit cytochrome P450. Another clinical study showed that anastrozole does not affect the pharmacokinetics of antipyrine (phenazone), so that it is unlikely to interact with those drugs which are known to be affected by enzyme inducers and inhibitors. 

Repetto L, Vannozzi 0, Hazini A, Sestini A, Pietropaolo M, Rosso R. Anastrozole and quinapril can be safely coadministered to elderly women with breast cancer and hypertension a pharmacokinetic study, Am Oncol (2003) 14, 1587-90. 

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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