Antunes Marina Venzon, de Oliveira Vanessa, Raymundo Suziane, Staudt Dilana Elisabeth, Gössling Gustavo, Biazús Jorge Villanova, Cavalheiro José Antônio, Rosa Daniela Dornelles, Mathy Geneviève, Wallemacq Pierre, Linden Rafael, Schwartsmann Gilberto, Haufroid Vincent
Pós-graduação em Ciências Médicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, n° 2400, 2nd floor, 90035-003, Porto Alegre, RS, Brazil.
Pharmacogenomics. 2015;16(6):601-17. doi: 10.2217/pgs.15.13. Epub 2015 Apr 20.
To evaluate the impact of CYP3A4*22 in the formation of endoxifen (EDF) and hydroxytamoxifen (HTF), under different CYP2D6 genotypic backgrounds.
MATERIALS & METHODS: 178 patients were enrolled in the study. CYP2D6 and CYP3A4 genotyping and tamoxifen (TAM) and metabolites quantification were performed.
EDF concentrations were lower in poor (2.77 ng ml(-1)) and CYP2D6 intermediate metabolizers (5.84 ng ml(-1)), comparing to functional group (EM-F) (10.67 ng ml(-1), p < 0.001). HTF and TAM levels were respectively 47 and 53% higher in CYP3A4*22 carriers compared with *1/1 patients in the whole group. Patients with impaired CYP2D6 metabolism and carriers of CYP3A422 had EDF levels comparable to CYP2D6 EM-F group (9.06 and 10.67 ng ml(-1), p = 0.247).
The presence of CYP3A4*22 might compensate the reduction of EDF concentrations related to CYP2D6 inactivity, especially due to increased HTF concentrations.
评估在不同CYP2D6基因背景下，CYP3A4*22对4-羟基他莫昔芬（EDF）和羟基他莫昔芬（HTF）形成的影响。
178例患者纳入本研究。进行CYP2D6和CYP3A4基因分型以及他莫昔芬（TAM）及其代谢产物定量分析。
与功能型组（EM-F）（10.67 ng/ml，p<0.001）相比，CYP2D6慢代谢型（2.77 ng/ml）和中间代谢型患者（5.84 ng/ml）的EDF浓度较低。在整个研究组中，CYP3A422携带者的HTF和TAM水平分别比1/1患者高47%和53%。CYP2D6代谢受损的患者和CYP3A422携带者的EDF水平与CYP2D6 EM-F组相当（9.06和10.67 ng/ml，p = 0.247）。
CYP3A4*22的存在可能补偿了因CYP2D6无活性导致的EDF浓度降低，尤其是由于HTF浓度升高。
