PDF(Pubmed)
Abstract：
UNASSIGNED: Carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2) are among the most abundant hydrolases in humans, catalyzing the metabolism of numerous clinically important medications, such as methylphenidate and clopidogrel. The large interindividual variability in the expression and activity of CES1 and CES2 affects the pharmacokinetics (PK) and pharmacodynamics (PD) of substrate drugs.
UNASSIGNED: This review provides an up-to-date overview of CES expression and activity regulations and examines their impact on the PK and PD of CES substrate drugs. The literature search was conducted on PubMed from inception to January 2024.
UNASSIGNED: Current research revealed modest associations of CES genetic polymorphisms with drug exposure and response. Beyond genomic polymorphisms, transcriptional and posttranslational regulations can also significantly affect CES expression and activity and consequently alter PK and PD. Recent advances in plasma biomarkers of drug-metabolizing enzymes encourage the research of plasma protein and metabolite biomarkers for CES1 and CES2, which could lead to the establishment of precision pharmacotherapy regimens for drugs metabolized by CESs. Moreover, our understanding of tissue-specific expression and substrate selectivity of CES1 and CES2 has shed light on improving the design of CES1- and CES2-activated prodrugs.
UNASSIGNED: This review provides an up-to-date overview of CES expression and activity regulations and examines their impact on the PK and PD of CES substrate drugs. The literature search was conducted on PubMed from inception to January 2024.
UNASSIGNED: Current research revealed modest associations of CES genetic polymorphisms with drug exposure and response. Beyond genomic polymorphisms, transcriptional and posttranslational regulations can also significantly affect CES expression and activity and consequently alter PK and PD. Recent advances in plasma biomarkers of drug-metabolizing enzymes encourage the research of plasma protein and metabolite biomarkers for CES1 and CES2, which could lead to the establishment of precision pharmacotherapy regimens for drugs metabolized by CESs. Moreover, our understanding of tissue-specific expression and substrate selectivity of CES1 and CES2 has shed light on improving the design of CES1- and CES2-activated prodrugs.
摘要：
■羧酸酯酶1（CES1）和羧酸酯酶2（CES2）是人类中最丰富的水解酶之一，催化许多临床上重要的药物的代谢，如哌醋甲酯和氯吡格雷。CES1和CES2的表达和活性的个体间差异很大，影响底物药物的药代动力学（PK）和药效学（PD）。
■这篇综述提供了CES表达和活性法规的最新概述，并考察了它们对CES底物药物的PK和PD的影响。文献检索从成立到2024年1月在PubMed上进行。
■目前的研究表明CES基因多态性与药物暴露和反应的适度关联。除了基因组多态性，转录和翻译后调控也可以显着影响CES的表达和活性，从而改变PK和PD。药物代谢酶的血浆生物标志物的最新进展促进了对CES1和CES2的血浆蛋白和代谢物生物标志物的研究，这可能导致建立CESs代谢药物的精确药物治疗方案。此外，我们对CES1和CES2的组织特异性表达和底物选择性的理解有助于改进CES1和CES2激活前药的设计.
■这篇综述提供了CES表达和活性法规的最新概述，并考察了它们对CES底物药物的PK和PD的影响。文献检索从成立到2024年1月在PubMed上进行。
■目前的研究表明CES基因多态性与药物暴露和反应的适度关联。除了基因组多态性，转录和翻译后调控也可以显着影响CES的表达和活性，从而改变PK和PD。药物代谢酶的血浆生物标志物的最新进展促进了对CES1和CES2的血浆蛋白和代谢物生物标志物的研究，这可能导致建立CESs代谢药物的精确药物治疗方案。此外，我们对CES1和CES2的组织特异性表达和底物选择性的理解有助于改进CES1和CES2激活前药的设计.
