Drug Metabolism and Pharmacokinetics最新文献_第3页

Human brain organoids for understanding substance use disorders 了解药物使用障碍的人脑器官模型

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-07-26 DOI: 10.1016/j.dmpk.2024.101031

引用次数: 0

Clinical pharmacokinetic characteristics of Jaktinib in subjects with hepatic impairment in a phase I trial I期试验中Jaktinib在肝功能受损受试者中的临床药代动力学特征

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-07-20 DOI: 10.1016/j.dmpk.2024.101030

Manna Zhao , Hua Zhang , Sheng Ma , Shuqing Gong , Cheng Wei , Liyan Miao , Weifeng Zhao

{"title":"Clinical pharmacokinetic characteristics of Jaktinib in subjects with hepatic impairment in a phase I trial","authors":"Manna Zhao , Hua Zhang , Sheng Ma , Shuqing Gong , Cheng Wei , Liyan Miao , Weifeng Zhao","doi":"10.1016/j.dmpk.2024.101030","DOIUrl":"10.1016/j.dmpk.2024.101030","url":null,"abstract":"<div><div>Jaktinib is a novel Janus kinase (JAK) inhibitor, and a phase I clinical trial of single-dose Jaktinib was conducted in a population of subjects with hepatic impairment to assess the safety, tolerability, and pharmacokinetic characteristics of Jaktinib. The patients were administered orally with 100 mg Jaktinib on day 1 in all the mild hepatic impairment group (mild group, n = 8), moderate hepatic impairment group (moderate group, n = 8) and normal hepatic function group (normal group, n = 8), and the blood samples were collected for later analysis. The mild to moderate hepatic impairment affected the metabolism of Jaktinib, which may lead to accumulation of original Jaktinib. The pharmacokinetic characteristics of the metabolites (ZG0244 and ZG0245) of Jaktinib were also analyzed. The exposure of Jaktinib is approximately 2-fold in patients with mild and moderate hepatic impairment than normal hepatic function. No serious adverse events occurred. In summary, a dosage reduction is recommended for patients with mild or moderate hepatic impairment. Further investigations for the dose adjustment in mild/moderate hepatic impairment will be considered. Trial registration number: NCT04993404.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"59 ","pages":"Article 101030"},"PeriodicalIF":2.7,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141843018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characteristics of membrane transport, metabolism, and target protein binding of cyclic depsipeptide destruxin E in HeLa cells 环去肽去甲芦荟素 E 在 HeLa 细胞中的膜转运、代谢和靶蛋白结合特性

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-07-02 DOI: 10.1016/j.dmpk.2024.101028

Makoto Amifuji , Mai Inagaki , Masahito Yoshida , Takayuki Doi , Masanori Tachikawa

{"title":"Characteristics of membrane transport, metabolism, and target protein binding of cyclic depsipeptide destruxin E in HeLa cells","authors":"Makoto Amifuji , Mai Inagaki , Masahito Yoshida , Takayuki Doi , Masanori Tachikawa","doi":"10.1016/j.dmpk.2024.101028","DOIUrl":"10.1016/j.dmpk.2024.101028","url":null,"abstract":"<div><p>Cyclic peptides have attracted attention as new modalities for drug development owing to their unique pharmacokinetic and pharmacodynamic properties. Destruxin E, a 19-membered cyclodepsipeptide, is a promising candidate drug for cancer therapy. The purpose of the present study was to clarify the molecular mechanisms underlying membrane transport, metabolism, and the binding for target molecules of destruxin E in human cervical carcinoma HeLa cells used as a model of cancer cells. The influx transport and the intracellular metabolism of destruxin E were non-saturable and saturable, respectively, at up to 10 μM. The intracellular amounts of destruxin E and destruxin E-diol after incubation of destruxin E with the cells significantly decreased at 4 °C compared to those at 37 °C. Destruxin E-diol, but not destruxin E, undergoes efflux transport out of cells via P-gp/MDR1/ABCB1 and BCRP/ABCG2. The epoxide hydrolase EPHX2 functions as a potent metabolizing enzyme that can convert the epoxide of destruxin E to the destruxin E-diol. Treatment with an EPHX2 inhibitor increased the intracellular destruxin E levels and enhanced the inhibitory activity of vacuolar type-H<sup>+</sup> ATPase. These results suggest that epoxide hydrolase could be a regulatory factor for intracellular destruxin E levels and its pharmacological activity.</p></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"58 ","pages":"Article 101028"},"PeriodicalIF":2.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141693654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preface: In silico technologies to facilitate drug development 前言促进药物开发的硅学技术

IF 2.1 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-06-01 DOI: 10.1016/j.dmpk.2024.101022

Kazuya Maeda Ph.D., Masayo Oishi Ph.D.

引用次数: 0

Beyond the basics: A deep dive into parameter estimation for advanced PBPK and QSP models 超越基础：深入了解高级 PBPK 和 QSP 模型的参数估计

IF 2.1 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-06-01 DOI: 10.1016/j.dmpk.2024.101011

Kota Toshimoto

{"title":"Beyond the basics: A deep dive into parameter estimation for advanced PBPK and QSP models","authors":"Kota Toshimoto","doi":"10.1016/j.dmpk.2024.101011","DOIUrl":"10.1016/j.dmpk.2024.101011","url":null,"abstract":"<div><p>Physiologically-based pharmacokinetic (PBPK) models and quantitative systems pharmacology (QSP) models have contributed to drug development strategies. The parameters of these models are commonly estimated by capturing observed values using the nonlinear least-squares method. Software packages for PBPK and QSP modeling provide a range of parameter estimation algorithms. To choose the most appropriate method, modelers need to understand the basic concept of each approach. This review provides a general introduction to the key points of parameter estimation with a focus on the PBPK and QSP models, and the respective parameter estimation algorithms. The latter part assesses the performance of five parameter estimation algorithms – the quasi-Newton method, Nelder-Mead method, genetic algorithm, particle swarm optimization, and Cluster Gauss-Newton method – using three examples of PBPK and QSP modeling. The assessment revealed that some parameter estimation results were significantly influenced by the initial values. Moreover, the choice of algorithms demonstrating good estimation results heavily depends on factors such as model structure and the parameters to be estimated. To obtain credible parameter estimation results, it is advisable to conduct multiple rounds of parameter estimation under different conditions, employing various estimation algorithms.</p></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"56 ","pages":"Article 101011"},"PeriodicalIF":2.1,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S134743672400017X/pdfft?md5=df144f44a617f6c8d8e5f084a82d4f42&pid=1-s2.0-S134743672400017X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140405620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DMPK perspective on quantitative model analysis for chimeric antigen receptor cell therapy: Advances and challenges 从 DMPK 角度看嵌合抗原受体细胞疗法的定量模型分析：进展与挑战

IF 2.1 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-06-01 DOI: 10.1016/j.dmpk.2024.101003

Akihiko Goto, Yuu Moriya, Miyu Nakayama, Shinji Iwasaki, Syunsuke Yamamoto

{"title":"DMPK perspective on quantitative model analysis for chimeric antigen receptor cell therapy: Advances and challenges","authors":"Akihiko Goto, Yuu Moriya, Miyu Nakayama, Shinji Iwasaki, Syunsuke Yamamoto","doi":"10.1016/j.dmpk.2024.101003","DOIUrl":"10.1016/j.dmpk.2024.101003","url":null,"abstract":"<div><p>Chimeric antigen receptor (CAR) cells are genetically engineered immune cells that specifically target tumor-associated antigens and have revolutionized cancer treatment, particularly in hematological malignancies, with ongoing investigations into their potential applications in solid tumors. This review provides a comprehensive overview of the current status and challenges in drug metabolism and pharmacokinetics (DMPK) for CAR cell therapy, specifically emphasizing on quantitative modeling and simulation (M&S). Furthermore, the recent advances in quantitative model analysis have been reviewed, ranging from clinical data characterization to mechanism-based modeling that connects <em>in vitro</em> and <em>in vivo</em> nonclinical and clinical study data. Additionally, the future perspectives and areas for improvement in CAR cell therapy translation have been reviewed. This includes using formulation quality considerations, characterization of appropriate animal models, refinement of <em>in vitro</em> models for bottom-up approaches, and enhancement of quantitative bioanalytical methodology. Addressing these challenges within a DMPK framework is pivotal in facilitating the translation of CAR cell therapy, ultimately enhancing the patients’ lives through efficient CAR cell therapies.</p></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"56 ","pages":"Article 101003"},"PeriodicalIF":2.1,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347436724000090/pdfft?md5=fbce09f1734f25402898ac010f89ccf3&pid=1-s2.0-S1347436724000090-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139873153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Population pharmacokinetic analysis of sirolimus in Japanese pediatric and adult subjects receiving tablet or granule formulations 西罗莫司在接受片剂或颗粒剂治疗的日本儿童和成人受试者中的群体药代动力学分析。

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-05-31 DOI: 10.1016/j.dmpk.2024.101024

Taichi Miyazaki , Daichi Hayashi , Akifumi Nozawa , Shiho Yasue , Saori Endo , Hidenori Ohnishi , Ryuta Asada , Mototoshi Kato , Akihiro Fujino , Tatsuo Kuroda , Takanobu Maekawa , Shigehisa Fumino , Naonori Kawakubo , Tatsuro Tajiri , Kenji Shimizu , Chihiro Sanada , Izumi Hamada , Yuko Ishikawa , Mayumi Hasegawa , Kashyap Patel , Michio Ozeki

{"title":"Population pharmacokinetic analysis of sirolimus in Japanese pediatric and adult subjects receiving tablet or granule formulations","authors":"Taichi Miyazaki , Daichi Hayashi , Akifumi Nozawa , Shiho Yasue , Saori Endo , Hidenori Ohnishi , Ryuta Asada , Mototoshi Kato , Akihiro Fujino , Tatsuo Kuroda , Takanobu Maekawa , Shigehisa Fumino , Naonori Kawakubo , Tatsuro Tajiri , Kenji Shimizu , Chihiro Sanada , Izumi Hamada , Yuko Ishikawa , Mayumi Hasegawa , Kashyap Patel , Michio Ozeki","doi":"10.1016/j.dmpk.2024.101024","DOIUrl":"10.1016/j.dmpk.2024.101024","url":null,"abstract":"<div><div>A population pharmacokinetic (PopPK) analysis was conducted using data from 215 Japanese administered oral sirolimus (tablet and granule) including healthy subjects and patients with intractable vascular anomalies and other diseases. The analysis included neonates, infants, and adults, and identified covariates that influence sirolimus pharmacokinetics (PK). The final model was used to predict sirolimus trough concentrations for various dosing regimens and covariates of interest. The results showed that sirolimus trough concentrations were predicted to increase with higher levels of hemoglobin, and that the granule formulation had a 1.23-fold higher exposure than the tablet formulation. Coadministration of CYP3A4 inducers was found to decrease trough concentrations by 54 %. The PK simulations showed that administration of the granule formulation at doses of 0.02, 0.04, 0.06, and 0.08 mg/kg/day in ages <3 months, 3 to <6 months, 6 to <12 months, and ≥1 year, respectively, resulted in >70 % target attainment within the therapeutic trough concentration range (5–15 ng/mL). In conclusion, incorporation of time-varying covariates (body weight and age) into the PopPK model appropriately predicted sirolimus concentrations in Japanese subjects from infants to adult sub-populations. This PopPK model would therefore be able to provide a reference for clinical individualization of sirolimus dosing.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"59 ","pages":"Article 101024"},"PeriodicalIF":2.7,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the human 3D small intestinal model (epiintestinaltm) for improved prediction of oral absorption, metabolism and complex drug-drug interactions of small molecule drugs 探索人体三维小肠模型（epiintestinaltm），以改进小分子药物的口服吸收、代谢和复杂的药物相互作用预测

IF 2.1 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-05-13 DOI: 10.1016/j.dmpk.2023.100908

Paresh Chothe, Andrea Whitcher-Johnstone, Niresh Hariparsad, Diane Ramsden

引用次数: 0

Plasma protein binding in special populations: do current PBPK models correctly account for potential changes to fraction unbound? 特殊人群的血浆蛋白结合：当前的 PBPK 模型是否正确地考虑了未结合部分的潜在变化？

IF 2.1 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-05-13 DOI: 10.1016/j.dmpk.2023.100976

Jokha Al-Qassabi, Shawn Tan, Aleksandra Galetin, Amin Rostami-Hodjegan, Daniel Scotcher

引用次数: 0

Understanding CYP3A4 and P-GP mediated drug-drug interactions through PBPK modeling - case example of pralsetinib 通过 PBPK 建模了解 CYP3A4 和 P-GP 介导的药物间相互作用--普拉塞替尼案例

IF 2.1 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-05-13 DOI: 10.1016/j.dmpk.2023.100969

Christine Bowman, Michael Dolton, Fang Ma, Sravanthi Cheeti, Denison Kuruvilla, Rucha Sane, Nastya Kassir, Yuan Chen

引用次数: 0