Breast cancer research and treatment · 2025
The impact of coadministration of venlafaxine, citalopram or gabapentin on the metabolic activation of tamoxifen.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Safgren Stephanie L, Suman Vera J, Leon Ferre Roberto A, Kosel Matthew L, Stearns Vered, Henry N Lynn, Denduluri Neelima, Irvin William, Ingle James N, Sideras Kostantinos, Ames Matthew M, Reid Joel M, Loprinzi Charles L, Black John L, Weinshilboum Richard M, Goetz Matthew P
Аннотация
PURPOSE: Tamoxifen undergoes metabolic activation by cytochrome P450 (CYP) enzymes to metabolites with more potent anti-estrogenic effects. Numerous studies demonstrate decreased tamoxifen efficacy associated with reduced CYP2D6 activity or lower Z-endoxifen concentrations. Women taking tamoxifen frequently experience vasomotor symptoms (VMS) that may require medical treatment. Many medications used for VMS or depression are CYP substrates that may reduce Z-endoxifen concentrations. While the drug-drug interactions (DDI) from potent CYP2D6 inhibitors (CYPi) on tamoxifen metabolism has been studied, the impact of less potent CYPi including drugs used to treat VMS remains largely unknown.
METHODS: We performed a prospective trial to evaluate the impact of gabapentin or non-potent CYPi (venlafaxine citalopram) on plasma concentrations of tamoxifen and its metabolites (Z-endoxifen, N-desmethyl-tamoxifen (NDMT) and 4-hydroxy-tamoxifen (4HT).
RESULTS: Patients enrolled were intermediate to extensive metabolizers by CYP2D6 genotyping. While tamoxifen and NDMT plasma concentrations were not significantly altered, the percent decrease in plasma Z-endoxifen concentration was statistically significant with the addition of venlafaxine (n = 22) or citalopram (n = 18) (median - 14.7 and - 14.4%, respectively) but not with gabapentin (n = 14) (median - 2.3%). A reduction in Z-endoxifen concentrations below the 5.9 ng/ml threshold associated with tamoxifen efficacy was observed in 12% of patients.
CONCLUSION: The addition of venlafaxine and citalopram but not gabapentin during tamoxifen treatment decreases plasma Z-endoxifen concentrations. SSRIs/SNRIs affecting tamoxifen biotransformation pathways, but with less potent CYPi potential, should be used cautiously in tamoxifen-treated patients and non-CYP inhibiting medications considered when possible.
METHODS: We performed a prospective trial to evaluate the impact of gabapentin or non-potent CYPi (venlafaxine citalopram) on plasma concentrations of tamoxifen and its metabolites (Z-endoxifen, N-desmethyl-tamoxifen (NDMT) and 4-hydroxy-tamoxifen (4HT).
RESULTS: Patients enrolled were intermediate to extensive metabolizers by CYP2D6 genotyping. While tamoxifen and NDMT plasma concentrations were not significantly altered, the percent decrease in plasma Z-endoxifen concentration was statistically significant with the addition of venlafaxine (n = 22) or citalopram (n = 18) (median - 14.7 and - 14.4%, respectively) but not with gabapentin (n = 14) (median - 2.3%). A reduction in Z-endoxifen concentrations below the 5.9 ng/ml threshold associated with tamoxifen efficacy was observed in 12% of patients.
CONCLUSION: The addition of venlafaxine and citalopram but not gabapentin during tamoxifen treatment decreases plasma Z-endoxifen concentrations. SSRIs/SNRIs affecting tamoxifen biotransformation pathways, but with less potent CYPi potential, should be used cautiously in tamoxifen-treated patients and non-CYP inhibiting medications considered when possible.