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• W2119591453 abstract "Rodent models of human breast cancer suggest that the combination of the steroidal aromatase inhibitor exemestane with tamoxifen may have additive activity. Clinical trials combining tamoxifen with letrozole or anastrazole have shown minor pharmacokinetic drug interactions. We did an open-label crossover clinical trial of the effect of exemestane on tamoxifen pharmacokinetics.Thirty-two postmenopausal women who were clinically disease-free following primary treatments for breast cancer receiving tamoxifen for at least 3 months were studied. Blood was collected for pharmacokinetic analysis after at least 4 months of receiving 20 mg tamoxifen daily. Subjects then began 8 weeks of oral exemestane (25 mg daily), followed by another set of blood samples.There were no serious toxicities noted when the two drugs were combined. There was no significant effect of exemestane on the area under the plasma concentration versus time curve (AUC) of tamoxifen at steady state before [3.04 mg h/L; 90% confidence interval (90% CI), 2.71-3.44] and during exemestane treatment (3.05 mg h/L; 90% CI, 2.72-3.41). There were no significant changes in the formation of primary tamoxifen metabolites. Oral clearance of exemestane averaged 602 L/h based on an average plasma exemestane AUC of 41.5 microg h/L (90% CI, 36.7-62.6). Plasma concentrations of estradiol, estrone, and estrone sulfate decreased when exemestane was begun; estradiol concentrations consistently decreased below the limit of quantitation.There is no pharmacokinetic interaction between tamoxifen and exemestane. No modification in the standard regimen of either drug seems to be indicated if they are used in combination. The combination of the two drugs was well tolerated during the 8-week evaluation period." @default.
• W2119591453 created "2016-06-24" @default.
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• W2119591453 date "2005-12-15" @default.
• W2119591453 modified "2023-09-27" @default.
• W2119591453 title "Effect of Exemestane on Tamoxifen Pharmacokinetics in Postmenopausal Women Treated for Breast Cancer" @default.
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• W2119591453 doi "https://doi.org/10.1158/1078-0432.ccr-05-0915" @default.
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