PDF(Pubmed)
Abstract：
Several population pharmacokinetic (PPK) models of B cell lymphoma-2 (BCL-2) venetoclax (VEN) have been developed and published to characterize the influencing factors of pharmacokinetics in hematologic malignancies. This review described PPK models of VEN examining the magnitude and types of covariate effects in PK parameters, as well as identified areas that require further investigation in order to facilitate their use. Currently, there are six analyses on PPK models of VEN summarized in this review. Most analyses described the pharmacokinetics of VEN with a two-compartment model and all covariates are categorical. The median estimated apparent clearance (CL/F) was 446 L/Day and apparent volume of distribution of the central compartment (V2/F) was 114.5 L. The median IIV of CL/F reported was 39.5% and V2/F was 46.7%. Most commonly, CYP3A inhibitors, OATP1B3 inhibitors and rituximab co-administration were found to be significant covariates on CL/F. In addition, sex and population were influential covariates on V2/F. A detailed description of the characteristics of PPK models of VEN is provided in this review, as well as the effects of covariates on the PK parameters. For future development of the VEN PPK model, CYP3A inhibitors, rituximab co-administration, OATP1B1 transporter inhibitors, sex, population, and food might be considered. Further research and comprehensive investigations should be undertaken to explore reference ranges for therapeutic drug monitoring, define the potential role of patients with cerebrospinal fluid complications, and assess new or potential covariates. These endeavors will facilitate the development of personalized VEN therapy.
摘要：
已经开发并发表了几种B细胞淋巴瘤2（BCL-2）维奈托克（VEN）的群体药代动力学（PPK）模型，以表征血液恶性肿瘤中药代动力学的影响因素。这篇综述描述了VEN的PPK模型，检查了PK参数中协变量效应的大小和类型，以及需要进一步调查以方便其使用的已确定区域。目前,这篇综述总结了六项关于VENPPK模型的分析。大多数分析用两室模型描述了VEN的药代动力学，所有协变量都是分类的。中值估计表观清除率(CL/F)为446L/天,并且中央隔室的表观分布体积(V2/F)为114.5L。报告的CL/F的中值IIV为39.5%,V2/F为46.7%。最常见的是,CYP3A抑制剂，发现OATP1B3抑制剂和利妥昔单抗共同给药是CL/F的重要协变量。此外,性别和人口是V2/F的影响协变量。这篇综述详细介绍了VEN的PPK模型的特点，以及协变量对PK参数的影响。对于VENPPK模型的未来发展，CYP3A抑制剂，利妥昔单抗联合用药，OATP1B1转运蛋白抑制剂，性别,人口,食物可以考虑。应进行进一步研究和全面调查，以探索治疗药物监测的参考范围，定义脑脊液并发症患者的潜在作用，并评估新的或潜在的协变量。这些努力将促进个性化VEN治疗的发展。
