Quiñones-Lombraña Adolfo, Li Nasi, Del Solar Virginia, Atilla-Gokcumen G Ekin, Blanco Javier G
University at Buffalo, The State University of New York (SUNY), Department of Pharmaceutical Sciences, Buffalo, New York, USA.
University at Buffalo, The State University of New York (SUNY), Department of Chemistry, Buffalo, New York, USA.
Biopharm Drug Dispos. 2018 Jun;39(6):315-318. doi: 10.1002/bdd.2135.
Loxoprofen is an anti-inflammatory drug that requires bioactivation into the trans-OH metabolite to exert pharmacological activity. Evidence suggests that carbonyl reductase 1 (CBR1) is important during the bioactivation of loxoprofen. This study examined the impact of the functional single nucleotide polymorphism CBR1 rs9024 on the bioactivation of loxoprofen in a collection of human liver samples. The synthesis ratios of trans-OH loxoprofen/cis-OH loxoprofen were 33% higher in liver cytosols from donors homozygous for the CBR1 rs9024 G allele in comparison with the ratios in samples from donors with heterozygous GA genotypes. Complementary studies examined the impact of CBR1 rs9024 on the bioactivation of loxoprofen in lymphoblastoid cell lines. CBR1 rs9024 genotype status impacts the synthesis of the bioactive trans-OH metabolite of loxoprofen in human liver.
洛索洛芬是一种抗炎药物，需要生物活化成反式-OH代谢物才能发挥药理活性。有证据表明，羰基还原酶1（CBR1）在洛索洛芬的生物活化过程中起重要作用。本研究在一组人类肝脏样本中检测了功能性单核苷酸多态性CBR1 rs9024对洛索洛芬生物活化的影响。与杂合子GA基因型供体的样本相比，CBR1 rs9024 G等位基因纯合子供体的肝脏胞质溶胶中反式-OH洛索洛芬/顺式-OH洛索洛芬的合成比率高33%。补充研究检测了CBR1 rs9024对淋巴母细胞系中洛索洛芬生物活化的影响。CBR1 rs9024基因型状态影响人类肝脏中洛索洛芬生物活性反式-OH代谢物的合成。
