Drug Metabolism and Pharmacokinetics最新文献

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Evaluation of OSTΑ/Β transporter activity on the basal membrane of CACO-2 cell monolayers 评估 CACO-2 细胞单层基底膜上 OSTΑ/Β 转运体的活性

IF 2.1 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2024-05-13 DOI: 10.1016/j.dmpk.2023.100991

Emi Yamaguchi, A. David Rodrigues, Emi Kimoto

引用次数: 0

Catabolites identification and quantification of antisense oligonucleotides by liquid chromatography - high resolution mass spectrometry (LC-HRMS) 利用液相色谱-高分辨质谱法（LC-HRMS）鉴定和定量反义寡核苷酸的代谢物

IF 2.1 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2024-05-13 DOI: 10.1016/j.dmpk.2023.100949

Xin Zhang, Khishig Tsogtbaatar, Mai Thayer, Ryan Takahashi

引用次数: 0

Endogenous metabolites change associated with pioglitazone administration in healthy male subjects 健康男性服用吡格列酮后的内源性代谢物变化

IF 2.1 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2024-05-13 DOI: 10.1016/j.dmpk.2023.100968

Jihyun Kang, SeungHwan Lee, Kyung-Sang Yu, Joo-Youn Cho

引用次数: 0

Physiologically based pharmacokinetic modeling of adeno-associated viruses and the transgene product 腺相关病毒和转基因产物的生理学药代动力学建模

IF 2.1 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2024-05-13 DOI: 10.1016/j.dmpk.2023.100974

Shufang Liu, Ekram Chowdhury, Guy Meno-Tetang, Dhaval Shah

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Utilization of target engagement in tissues measured by immunoaffinity LC-MS/MS for PBPK modeling of monoclonal antibody 利用免疫亲和力 LC-MS/MS 测定的组织中的目标参与度建立单克隆抗体的 PBPK 模型

IF 2.1 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2024-05-13 DOI: 10.1016/j.dmpk.2023.100972

Yutaro Hoshi, Yuki Oda, Junji Komaba, Yoshiyuki Yamaura

引用次数: 0

Investigating cross-species differences of MDR1-mediated drug transport 调查 MDR1 介导的药物转运的跨物种差异

IF 2.1 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2024-05-13 DOI: 10.1016/j.dmpk.2023.100983

Csilla Temesszentandrasi-Ambrus, Krisztina Heredi-Szabo, Emoke Soskuti, Nora Szilvasy, Emese Kis, Zsuzsanna Gaborik

引用次数: 0

Synthesis and characterization of human metabolites of the echinocandid drug rezafungin by microbial biotransformation 通过微生物生物转化合成棘白类药物雷沙芬净的人体代谢物并确定其特征

IF 2.1 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2024-05-13 DOI: 10.1016/j.dmpk.2023.100942

Julia Shanu-Wilson, Ravi Manohar, Adriana Gomez, Richard Phipps, Jonathan Steele, Stephen Wrigley, Liam Evans, Frank Scheffler

引用次数: 0

Challenges in PBPK modeling of phenolic drugs extensively metabolized by intestinal phase II enzyme 酚类药物经肠道二期酶广泛代谢的 PBPK 建模难题

IF 2.1 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2024-05-13 DOI: 10.1016/j.dmpk.2023.100977

Rashim Singh, Ming Hu, Lu Wang, Yifan Tu

引用次数: 0

Insights into drug development with quantitative systems pharmacology: A prospective case study of uncovering hyperkalemia risk in diabetic nephropathy with virtual clinical trials 用定量系统药理学洞察药物开发：利用虚拟临床试验揭示糖尿病肾病高钾血症风险的前瞻性案例研究

IF 2.1 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2024-05-09 DOI: 10.1016/j.dmpk.2024.101019

Ryuta Saito, Tomohisa Nakada

The quantitative systems pharmacology (QSP) approach is widely applied to address various essential questions in drug discovery and development, such as identification of the mechanism of action of a therapeutic agent, patient stratification, and the mechanistic understanding of the progression of disease. In this review article, we show the current landscape of the application of QSP modeling using a survey of QSP publications over 10 years from 2013 to 2022. We also present a use case for the risk assessment of hyperkalemia in patients with diabetic nephropathy treated with mineralocorticoid receptor antagonists (MRAs, renin-angiotensin-aldosterone system inhibitors), as a prospective simulation of late clinical development. A QSP model for generating virtual patients with diabetic nephropathy was used to quantitatively assess that the nonsteroidal MRAs, finerenone and apararenone, have a lower risk of hyperkalemia than the steroidal MRA, eplerenone. Prospective simulation studies using a QSP model are useful to prioritize pharmaceutical candidates in clinical development and validate mechanism-based pharmacological concepts related to the risk-benefit, before conducting large-scale clinical trials.

定量系统药理学（QSP）方法被广泛应用于解决药物发现和开发中的各种基本问题，如确定治疗药物的作用机制、患者分层以及从机理上理解疾病的进展。在这篇综述文章中，我们通过对 2013 年至 2022 年这 10 年间发表的 QSP 论文进行调查，展示了 QSP 建模应用的现状。我们还介绍了糖尿病肾病患者使用矿物质皮质激素受体拮抗剂（MRAs，肾素-血管紧张素-醛固酮系统抑制剂）治疗高钾血症的风险评估用例，作为后期临床开发的前瞻性模拟。使用 QSP 模型生成糖尿病肾病虚拟患者，以定量评估非甾体类 MRA（非格列酮和阿帕瑞酮）比甾体类 MRA（依普列酮）发生高钾血症的风险更低。在进行大规模临床试验之前，使用 QSP 模型进行前瞻性模拟研究有助于确定临床开发候选药物的优先次序，并验证与风险-效益相关的基于机制的药理学概念。

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引用次数: 0

Practical QSP application from the preclinical phase to enhance the probability of clinical success: Insights from case studies in oncology 从临床前阶段开始实际应用 QSP，提高临床成功的概率：肿瘤学案例研究的启示

IF 2.1 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2024-05-09 DOI: 10.1016/j.dmpk.2024.101020

Masayo Oishi , Hiroyuki Sayama , Kota Toshimoto , Takeshi Nakayama , Yasuhisa Nagasaka

Quantitative Systems Pharmacology (QSP) has emerged as a promising modeling and simulation (M&S) approach in drug development, with potential to improve clinical success rates. While conventional M&S has significantly contributed to quantitative understanding in late preclinical and clinical phases, it falls short in explaining unexpected phenomena and testing hypotheses in the early research phase. QSP presents a solution to these limitations. To harness the full potential of QSP in early preclinical stages, preclinical modelers who are familiar with conventional M&S need to update their understanding of the differences between conventional M&S and QSP. This review focuses on QSP applications during the preclinical stage, citing case examples and sharing our experiences in oncology. We emphasize the critical role of QSP in increasing the probability of success for clinical proof of concept (PoC) when applied from the early preclinical stage. Enhancing the quality of both hypotheses and QSP models from early preclinical stage is of critical importance. Once a QSP model achieves credibility, it facilitates predictions of clinical responses and potential biomarkers. We propose that sequential QSP applications from preclinical stages can improve success rates of clinical PoC, and emphasize the importance of refining both hypotheses and QSP models throughout the process.

定量系统药理学（QSP）已成为药物开发中一种前景广阔的建模与模拟（M&S）方法，具有提高临床成功率的潜力。虽然传统的 M&S 对临床前和临床后期的定量理解做出了重大贡献，但在解释早期研究阶段的意外现象和测试假设方面却存在不足。QSP 为解决这些局限性提供了解决方案。为了充分发挥 QSP 在临床前早期阶段的潜力，熟悉传统 M&S 的临床前建模人员需要更新他们对传统 M&S 与 QSP 之间差异的认识。本综述将重点讨论 QSP 在临床前阶段的应用，引用案例并分享我们在肿瘤学方面的经验。我们强调 QSP 在临床前早期阶段的应用对提高临床概念验证 (PoC) 成功概率的关键作用。从早期临床前阶段开始提高假设和 QSP 模型的质量至关重要。一旦 QSP 模型达到可信度，它就能促进对临床反应和潜在生物标记物的预测。我们建议，从临床前阶段开始依次应用 QSP 可以提高临床 PoC 的成功率，并强调在整个过程中完善假设和 QSP 模型的重要性。

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引用次数: 0

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