Aim The aim of this study was to evaluate the pharmacogenetic variability in the disposition of felodip- ine in healthy Chinese subjects. Methods A single oral dose of 5 mg felodipine was orally administered to 45 hea...Aim The aim of this study was to evaluate the pharmacogenetic variability in the disposition of felodip- ine in healthy Chinese subjects. Methods A single oral dose of 5 mg felodipine was orally administered to 45 healthy Chinese subjects. The serum concentrations of felodipine were measured by using LC/MS/MS. We detected the SNPs of CYP450 enzymes and transporters, which play vital roles in drug metabolism and are with a high fre- quency of mutation in Chinese. Results The area under the plasma concentration - time curve （AUC） within the time points 0 to 72 h （AUC（0-72） ） after felodipine administration was significantly higher in the subjects possessing the CYP3A5 ＊ 1/＊ 3 alleles than in those with the CYP3A5 ＊ 1/＊ 1 alleles （P =0. 021 ）. The BCRP 421A allele was associated with a trend of reduced pharmacokinetic exposure （P = 0. 034）. The mean Tmax in subjects with the CYP3A4 ＊ 1/＊ 18B carriers was longer than in those with the CYP3A4 ＊ 1/＊ 1. The pharmacokinetics charac- teristics of felodipine were not associated with other SNPs we investigated. Conclusion This study showed that the genetic polymorphisms of CYP3A5＊ 3 and BCRPC421A might explain the variability in the pharmacokinetics of felodipine in the Chinese population.展开更多
目的 探讨微核糖核酸-525-5p(mi R-525-5p)、围脂滴蛋白3(PLIN3)的表达与胶质瘤预后的关系。方法选取2018年2月至2020年7月青岛市市立医院收治的102例胶质瘤患者,收集术中部分瘤组织和瘤旁组织采用实时荧光定量聚合酶链式反应检测mi R-5...目的 探讨微核糖核酸-525-5p(mi R-525-5p)、围脂滴蛋白3(PLIN3)的表达与胶质瘤预后的关系。方法选取2018年2月至2020年7月青岛市市立医院收治的102例胶质瘤患者,收集术中部分瘤组织和瘤旁组织采用实时荧光定量聚合酶链式反应检测mi R-525-5p、PLIN3 m RNA表达,免疫组织化学染色法检测PLIN3表达。通过Target Scan数据库预测mi R-525-5p与PLIN3的结合位点,分析二者在胶质瘤组织中表达的相关性。根据胶质瘤组织中PLIN3 m RNA表达均值分为高表达组和低表达组,采用Kaplan-Meier法绘制高/低PLIN3 m RNA表达胶质瘤患者生存曲线,多因素Cox回归分析胶质瘤患者预后影响因素。结果 与瘤旁组织比较,胶质瘤组织中mi R-525-5p表达降低,PLIN3 m RNA表达升高(P<0.05)。与瘤旁组织比较,胶质瘤组织中PLIN3阳性率升高(P<0.05)。mi R-525-5p与PLIN3存在结合位点。mi R-525-5p与PLIN3 m RNA表达在胶质瘤组织中呈负相关(P<0.05)。PLIN3 m RNA高表达组3年总生存率低于低表达组(P<0.05)。多因素Cox回归分析显示,低分化、世界卫生组织中枢神经系统肿瘤分级Ⅲ~Ⅳ级、PLIN3 m RNA≥1.86为胶质瘤患者死亡的独立危险因素(HR>1,P<0.05)。结论 胶质瘤组织中mi R-525-5p低表达和PLIN3 m RNA高表达,二者表达呈负相关,PLIN3 m RNA高表达与胶质瘤患者预后不良有关。展开更多
文摘Aim The aim of this study was to evaluate the pharmacogenetic variability in the disposition of felodip- ine in healthy Chinese subjects. Methods A single oral dose of 5 mg felodipine was orally administered to 45 healthy Chinese subjects. The serum concentrations of felodipine were measured by using LC/MS/MS. We detected the SNPs of CYP450 enzymes and transporters, which play vital roles in drug metabolism and are with a high fre- quency of mutation in Chinese. Results The area under the plasma concentration - time curve （AUC） within the time points 0 to 72 h （AUC（0-72） ） after felodipine administration was significantly higher in the subjects possessing the CYP3A5 ＊ 1/＊ 3 alleles than in those with the CYP3A5 ＊ 1/＊ 1 alleles （P =0. 021 ）. The BCRP 421A allele was associated with a trend of reduced pharmacokinetic exposure （P = 0. 034）. The mean Tmax in subjects with the CYP3A4 ＊ 1/＊ 18B carriers was longer than in those with the CYP3A4 ＊ 1/＊ 1. The pharmacokinetics charac- teristics of felodipine were not associated with other SNPs we investigated. Conclusion This study showed that the genetic polymorphisms of CYP3A5＊ 3 and BCRPC421A might explain the variability in the pharmacokinetics of felodipine in the Chinese population.
文摘目的 探讨微核糖核酸-525-5p(mi R-525-5p)、围脂滴蛋白3(PLIN3)的表达与胶质瘤预后的关系。方法选取2018年2月至2020年7月青岛市市立医院收治的102例胶质瘤患者,收集术中部分瘤组织和瘤旁组织采用实时荧光定量聚合酶链式反应检测mi R-525-5p、PLIN3 m RNA表达,免疫组织化学染色法检测PLIN3表达。通过Target Scan数据库预测mi R-525-5p与PLIN3的结合位点,分析二者在胶质瘤组织中表达的相关性。根据胶质瘤组织中PLIN3 m RNA表达均值分为高表达组和低表达组,采用Kaplan-Meier法绘制高/低PLIN3 m RNA表达胶质瘤患者生存曲线,多因素Cox回归分析胶质瘤患者预后影响因素。结果 与瘤旁组织比较,胶质瘤组织中mi R-525-5p表达降低,PLIN3 m RNA表达升高(P<0.05)。与瘤旁组织比较,胶质瘤组织中PLIN3阳性率升高(P<0.05)。mi R-525-5p与PLIN3存在结合位点。mi R-525-5p与PLIN3 m RNA表达在胶质瘤组织中呈负相关(P<0.05)。PLIN3 m RNA高表达组3年总生存率低于低表达组(P<0.05)。多因素Cox回归分析显示,低分化、世界卫生组织中枢神经系统肿瘤分级Ⅲ~Ⅳ级、PLIN3 m RNA≥1.86为胶质瘤患者死亡的独立危险因素(HR>1,P<0.05)。结论 胶质瘤组织中mi R-525-5p低表达和PLIN3 m RNA高表达,二者表达呈负相关,PLIN3 m RNA高表达与胶质瘤患者预后不良有关。
