更新于：2024-11-01

POR x P-gp

更新于：2024-11-01

基本信息

关联

项与 POR x P-gp 相关的药物

ATHX-04

靶点

P-gp x POR

作用机制

P-gp抑制剂 [+1]

在研机构-

原研机构

Athenex, Inc.

在研适应症-

非在研适应症

肿瘤

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 POR x P-gp 相关的临床结果

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100 项与 POR x P-gp 相关的转化医学

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0 项与 POR x P-gp 相关的专利（医药）

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项与 POR x P-gp 相关的文献（医药）

2024-04-02·Journal of Chemotherapy

Combined impact of hypoalbuminemia and pharmacogenomic variants on voriconazole trough concentration: data from a real-life clinical setting in the Chinese population

Article

作者: Liu, Fang ; Hao, Xu ; Li, Yuanyuan ; Huang, Lin ; Yang, Changqing ; Bian, Jialu ; Liu, Boyu ; Hu, Lei ; Zhao, Jinxia ; Zhao, Yinyu ; Feng, Yufei ; Zhang, Ying

Voriconazole (VRC) displays highly variable pharmacokinetics impacting treatment efficacy and safety. To provide evidence for optimizing VRC therapy regimens, the authors set out to determine the factors impacting VRC steady-state trough concentration (C_min) in patients with various albumin (Alb) level. A total of 275 blood samples of 120 patients and their clinical characteristics and genotypes of CYP2C19, CYP3A4, CYP3A5, CYP2C9, FMO3, ABCB1, POR, NR1I2 and NR1I3 were included in this study. Results of multivariate linear regression analysis demonstrated that C-reactive protein (CRP) and total bilirubin (T-Bil) were predictors of the VRC C_min adjusted for dose in patients with hypoalbuminemia (Alb < 35 g/L) (R² = 0.16, P < 0.001). Additionally, in patients with normal albumin level (Alb ≥ 35 g/L), it resulted in a significant model containing factors of the poor metabolizer (PM) CYP2C19 genotype and CRP level (R² = 0.26, P < 0.001). Therefore, CRP and T-Bil levels ought to receive greater consideration than genetic factors in patients with hypoalbuminemia.

2024-02-01·The Pharmacogenomics Journal

The pharmacogenetics of tacrolimus in renal transplant patients: association with tremors, new-onset diabetes and other clinical events

Article

作者: Chouchene, Saoussen ; Khalij, Yassine ; Abbes, Houwaida ; Amor, Dorra ; Abderahmene, Amani ; Moussa, Amira ; Ganouni, Mohamed Rayen ; Zellama, Dorsaf ; Omezzine, Asma ; Bouslama, Ali ; Ammar, Meriam ; Sahtout, Wissal ; Ellouz, Amel

Our study is the first study to investigate the effect of SNPs in CYP3A5, CYP3A4, ABCB1 and POR genes on the incidence of tremors, nephrotoxicity, and diabetes mellitus. A total of 223 renal transplant patients receiving tacrolimus and mycophenolate mofetil (MMF) were recruited. Both adults and children patients participated in the study. Genotyping was performed using PROFLEX-PCR followed by RFLP. MPA and tacrolimus plasma concentrations were measured by immunoassay. The AUC0-12h of MMF was estimated by a Bayesian method. We found a statistically significant association between the CYP3A5*3 and CYP3A4*1B genotypes and the tacrolimus exposure. We found a lower occurrence of nephrotoxicity (p = 0.03), tremor (p = 0.01), and new-onset diabetes (p = 0.002) associated with CYP3A5*1 allele. The CYP3A4*1B allele was significantly associated with a lower occurrence of new-onset diabetes (p = 0.026). The CYP3A5*1 allele was significantly associated with an increased risk of acute and chronic rejection (p = 0.03 and p < 0.001, respectively). Our results support the usefulness of tacrolimus pharmacokinetics in pre-kidney transplant assessments.

2023-11-01·Cancer chemotherapy and pharmacology

Population pharmacokinetics and pharmacogenetics analyses of imatinib in Chinese patients with chronic myeloid leukemia in a real-world situation.

Article

作者: Zhao, Jinxia ; Shao, Qianhang ; Bian, Jialu ; Hao, Xu ; Jiang, Qian ; He, Shiyu ; Huang, Lin ; Liu, Boyu ; Hu, Lei ; He, Huan ; Zhao, Yinyu ; Li, Yuanyuan

BACKGROUNDImatinib is presently the first-line choice for the treatment of chronic myeloid leukemia. However, there are limited real-world data on Chinese patients to support individualized medicine. This work aims to characterize population pharmacokinetics in Chinese patients with chronic myeloid leukemia, investigate the effects of several covariates on imatinib exposure, and provide support for personalized medicine and dose reduction.METHODSA total of 230 patients with chronic myeloid leukemia were enrolled, and 424 steady-state concentration measurements were taken to perform the population pharmacokinetic analysis and Monte Carlo simulations with Phoenix NLME software. The effects of the demographic, biological, and pharmacogenetic (ten SNP corresponding to CYP3A4, CYP3A5, ABCB1, ABCG2, SCL22A1 and POR) covariates on clearance were evaluated.RESULTSA one-compartmental model best-described imatinib pharmacokinetics. The hemoglobin and the estimated glomerular filtration rate (< 85 mL⋅min^-1⋅1.73 m²) were associated with imatinib clearance. The genetic polymorphisms related to pharmacokinetics were not found to have a significant effect on the clearance of imatinib. The final model estimates of parameters are: k_a (h^-1) = 0.329; V_d/F (L) = 270; CL/F (L⋅h^-1) = 7.60.CONCLUSIONSKey covariates in the study population accounting for variability in imatinib exposure are hemoglobin and the estimated glomerular filtration rate. There is some need for caution when treating patients with moderate-to-severe renal impairment and significant hemoglobin changes.