Drug Metabolism and Pharmacokinetics最新文献_第2页

Global expansion of microphysiological systems (MPS) and Japan's initiatives: Innovation in pharmaceutical development and path to regulatory acceptance

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2025-02-01 DOI: 10.1016/j.dmpk.2024.101047

Daiju Yamazaki , Seiichi Ishida

{"title":"Global expansion of microphysiological systems (MPS) and Japan's initiatives: Innovation in pharmaceutical development and path to regulatory acceptance","authors":"Daiju Yamazaki , Seiichi Ishida","doi":"10.1016/j.dmpk.2024.101047","DOIUrl":"10.1016/j.dmpk.2024.101047","url":null,"abstract":"<div><div>Microphysiological systems (MPS) are gaining global attention as potential game-changers in pharmaceutical development. Since 2013, MPS suppliers from university laboratories in the United States and Europe have competed to develop these devices. After the development phase, the focus shifted to the accumulation of applications using MPS for pharmaceutical companies and end users. In Japan, the AMED-MPS project was launched in 2017, and since then, several MPS devices have been marketed by project participated suppliers. Initially, while Japanese pharmaceutical companies adopted foreign products, they also exhibited interest in domestically produced MPS devices. The utilization of new approach methodologies, including MPS, is expanding in the field of chemical substances risk assessment, and the Organization for Economic Co-operation and Development test guidelines are expected to adopt <em>in vitro</em> evaluation systems as alternatives to animal testing. This publication reviews global and Japanese trends surrounding MPS and outlines activities aimed at the regulatory acceptance of MPS as evaluation systems for medical drugs and chemicals.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"60 ","pages":"Article 101047"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028109","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

Effect of obesity on pharmacokinetics of transdermal fentanyl: Single-center retrospective study and animal study 肥胖对芬太尼透皮药代动力学的影响：单中心回顾性研究和动物研究。

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2025-02-01 DOI: 10.1016/j.dmpk.2024.101035

Satoshi Mizuno , Shintaro Gake , Makiko Takabayashi , Yuriko Ito , Hiroko Sanada , Natsumi Sugimoto , Akari Maeda , Takuto Tamamura , Kazuki Sawamoto , Yusuke Hara , Yoshiko Ohi , Chiaki Tsuji , Yukiko Shiomoto , Yukio Kato , Arimi Fujita , Tsutomu Shimada , Ken-ichi Miyamoto , Yoshimichi Sai

{"title":"Effect of obesity on pharmacokinetics of transdermal fentanyl: Single-center retrospective study and animal study","authors":"Satoshi Mizuno , Shintaro Gake , Makiko Takabayashi , Yuriko Ito , Hiroko Sanada , Natsumi Sugimoto , Akari Maeda , Takuto Tamamura , Kazuki Sawamoto , Yusuke Hara , Yoshiko Ohi , Chiaki Tsuji , Yukiko Shiomoto , Yukio Kato , Arimi Fujita , Tsutomu Shimada , Ken-ichi Miyamoto , Yoshimichi Sai","doi":"10.1016/j.dmpk.2024.101035","DOIUrl":"10.1016/j.dmpk.2024.101035","url":null,"abstract":"<div><div>A retrospective study and an animal study were conducted to investigate factors affecting the transdermal fentanyl dose to achieve adequate pain relief in patients switched from other opioids. In the retrospective study, patient factors were included as gender, age, body mass index (BMI), and serum albumin concentration. In obese (BMI ≥25) patients, the post-titration dose of transdermal fentanyl was significantly lower than in normal (BMI 18.5–25) patients despite the initial dose was the same. To support this unexpected finding, fentanyl was administered intravenously and transdermally to Zucker (<em>fa</em>/<em>fa</em>) rats as an obese model and Zucker (<em>+</em>/<em>+</em>) rats as a control. No difference in systemic clearance (<em>CL</em><sub>tot</sub>) after intravenous administration was observed between the two groups. However, transdermal bioavailability (<em>F</em>) and fentanyl release ratio from the formulation (<em>F</em><sub>a</sub>) were significantly increased in Zucker (<em>fa</em>/<em>fa</em>) rats compared to Zucker (<em>+</em>/<em>+</em>) rats. Skin availability (<em>F</em><sub>skin</sub>), calculated as <em>F</em> divided by <em>F</em><sub>a</sub>, was also significantly increased. These results indicated that obesity should be considered as a factor in the titration of transdermal fentanyl dose.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"60 ","pages":"Article 101035"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853519","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

Human brain organoids for understanding substance use disorders 用于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 : 2025-02-01 DOI: 10.1016/j.dmpk.2024.101036

Kangle Li , Longjun Gu , Hongwei Cai , Hui-Chen Lu , Ken Mackie , Feng Guo

{"title":"Human brain organoids for understanding substance use disorders","authors":"Kangle Li , Longjun Gu , Hongwei Cai , Hui-Chen Lu , Ken Mackie , Feng Guo","doi":"10.1016/j.dmpk.2024.101036","DOIUrl":"10.1016/j.dmpk.2024.101036","url":null,"abstract":"<div><div>Substance use disorders (SUDs) are complex mental health conditions involving a problematic pattern of substance use. Challenges remain in understanding its neural mechanisms, which are likely to lead to improved SUD treatments. Human brain organoids, brain-like 3D in vitro cultures derived from human stem cells, show unique potential in recapitulating the response of a developing human brain to substances. Here, we review the recent progress in understanding SUD using human brain organoid models focusing on neurodevelopmental perspectives. We first summarize the background of SUD in humans. Moreover, we introduce the development of various human brain organoid models and then discuss current progress and findings underlying the abuse of substances like nicotine, alcohol, and other addictive drugs using organoid models. Furthermore, we review efforts to develop organ chips and microphysiological systems to engineer better human brain organoids for advancing SUD studies. Lastly, we conclude by elaborating on the current challenges and future directions of SUD studies using human brain organoids.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"60 ","pages":"Article 101036"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681198","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

The refined CYP2B6-Template system for studies of its ligand metabolisms 改良的cyp2b6 -模板系统用于其配体代谢的研究。

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2025-02-01 DOI: 10.1016/j.dmpk.2024.101037

Yasushi Yamazoe , Kouichi Yoshinari

{"title":"The refined CYP2B6-Template system for studies of its ligand metabolisms","authors":"Yasushi Yamazoe , Kouichi Yoshinari","doi":"10.1016/j.dmpk.2024.101037","DOIUrl":"10.1016/j.dmpk.2024.101037","url":null,"abstract":"<div><div>The previously reported Template system for the prediction of human CYP2B6-mediated reactions (Drug Metab Pharmacokinet 26 309–330, 2011) has been refined with the introduction of ideas of allowable width, Trigger-residue and the residue-initiated movement of ligands in the active site. The refined system also includes ideas of bi-molecule binding on Template. With the use of these ideas in common with other Template systems for human CYP1A1, CYP1A2, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2E1, and CYP3A4, 360 reactions of 261 distinct chemicals reported as CYP2B6 ligands were examined in the refined system. From their placements on the refined Template and rules for interaction modes, verifications of good and poor substrates, regio- and stereo-selectivities, and inhibitory interaction became faithfully available for these ligands, in which all the chemicals tested in the previous study were included. From the comparison of substrate specificities of human CYP2B6 and rat CYP2B1, size differences of one of the enzyme residues, Shelf, were suggested as a cause of their distinct catalyses. The refined CYP2B6-Template system will thus offer more reliable estimations of this human CYP catalyses toward ligands of diverse structures, together with their deciphering information to lead to judgments of metabolisms.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"60 ","pages":"Article 101037"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964271","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

Opportunities for microphysiological systems from the view of Japanese industries

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2025-02-01 DOI: 10.1016/j.dmpk.2024.101034

Hitoshi Naraoka, Takuma Iguchi, Kosuke Harada, Toru Usui, Yoshiaki Suwa, Masamitsu Ando, Takeshi Sakura, Tomoki Ohkubo

引用次数: 0

Micro-physiological system of human lung: The current status and application to drug discovery

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2025-02-01 DOI: 10.1016/j.dmpk.2024.101050

Naoyuki Sone, Shimpei Gotoh

{"title":"Micro-physiological system of human lung: The current status and application to drug discovery","authors":"Naoyuki Sone, Shimpei Gotoh","doi":"10.1016/j.dmpk.2024.101050","DOIUrl":"10.1016/j.dmpk.2024.101050","url":null,"abstract":"<div><div>Various attempts have been made to elucidate the mechanisms of human lung development, its physiological functions, and diseases, in the hope of new drug discovery. Recent technological advancements in experimental animals, cell culture, gene editing, and analytical methods have provided new insights and therapeutic strategies. However, the results obtained from animal experiments are often inconsistent with those obtained from human data because of reproducibility issues caused by structural and physiological differences between mice and humans. In addition, it is not possible to accurately reproduce the internal environment of the human lung structure using conventional two-dimensional (2D) or three-dimensional (3D) cell culture methods. As a result, the micro-physiological system (MPS) technology, such as “lung-on-a-chip” that can culture human cells in a state close to human body environment have been developed, and its applications to disease models, toxicological studies, and drug discovery are accelerated worldwide. Here, we focus on the mimetics of the lung, including “lung-on-a-chip” technology, and review their recent progress, achievements and challenges. Finally, we discuss the role of these chips in drug discovery for refractory lung diseases.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"60 ","pages":"Article 101050"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028202","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

In vitro hydrolysis of areca nut xenobiotics in human liver 槟榔异种制剂在人肝脏中的体外水解研究。

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2025-02-01 DOI: 10.1016/j.dmpk.2024.101039

Vincenzo Paolillo , Mahendran Jayakumar , Colton Sheperd , Andrew Tran , Stephanie Hoang , Nhu Dao , Parag Jain , Alan L. Myers

{"title":"In vitro hydrolysis of areca nut xenobiotics in human liver","authors":"Vincenzo Paolillo , Mahendran Jayakumar , Colton Sheperd , Andrew Tran , Stephanie Hoang , Nhu Dao , Parag Jain , Alan L. Myers","doi":"10.1016/j.dmpk.2024.101039","DOIUrl":"10.1016/j.dmpk.2024.101039","url":null,"abstract":"<div><div>Areca nut (AN) is a substance of abuse consumed by millions worldwide, in spite of established oral and systemic toxicities associated with its use. Previous research demonstrates methyl ester alkaloids in the AN, such as arecoline and guvacoline, exhibit mood-altering and toxicological effects. Nonetheless, their metabolism has not been fully elucidated in humans. In the present study, an HPLC-UV bioanalytical method was developed to evaluate the hydrolytic kinetics and clearance rates of arecoline and guvacoline in human liver microsomes (HLM) and cytosol (HLC). The bioassay was capable of quantifying arecoline and guvacoline (and carboxylate metabolites arecaidine and guvacine, respectively) with good sensitivity, accuracy, and precision. Kinetics of arecoline and guvacoline hydrolysis best followed the Michaelis-Menten model. Apparent intrinsic clearance (Cl<sub>int.<em>in vivo</em></sub>) of arecoline was 57.8 ml/min/kg in HLM and 11.6 mL/min/kg in HLC, a 5-fold difference. Unexpectedly, guvacoline was dramatically less hydrolyzed than arecoline in both HLM and HLC, with Cl<sub>int.<em>in vivo</em></sub> estimates of 0.654 ml/min/kg and 0.466 ml/min/kg, respectively. These results demonstrate, for the first time, arecoline undergoes significant hydrolysis with high clearance rates in the liver. Furthermore, differential tissue metabolic rates and utilization of specific esterase inhibitors unequivocally demonstrated arecoline is a substrate for CES1 and not CES2.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"60 ","pages":"Article 101039"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817247","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 and exposure-response analysis to support a dosing regimen of CPX-351 (NS-87) in Japanese adult and pediatric patients with untreated high-risk acute myeloid leukemia 人群药代动力学和暴露反应分析支持CPX-351 （NS-87）在日本成人和儿童未经治疗的高危急性髓性白血病患者中的给药方案。

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2025-02-01 DOI: 10.1016/j.dmpk.2024.101038

Shunji Imai , Ayane Kitada , Aya Ogura , Michiyo Akagi , Mayumi Hasegawa , Grygoriy Vasilinin , J.F. Marier , Qi Wang , Tomohiko Ichikawa , Kazutomi Kusano

{"title":"Population pharmacokinetic and exposure-response analysis to support a dosing regimen of CPX-351 (NS-87) in Japanese adult and pediatric patients with untreated high-risk acute myeloid leukemia","authors":"Shunji Imai , Ayane Kitada , Aya Ogura , Michiyo Akagi , Mayumi Hasegawa , Grygoriy Vasilinin , J.F. Marier , Qi Wang , Tomohiko Ichikawa , Kazutomi Kusano","doi":"10.1016/j.dmpk.2024.101038","DOIUrl":"10.1016/j.dmpk.2024.101038","url":null,"abstract":"<div><div>CPX-351 (NS-87; Vyxeos®) has a characteristic liposomal formulation and contains cytarabine and daunorubicin at a 5:1 molar ratio, which demonstrates synergistic activity in both <em>in vitro</em> and <em>in vivo</em> animal models. It has been approved in several countries for the treatment of newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). Since there are very few Asian patients, especially Japanese adult and pediatric patients, only a small clinical study has been conducted in Japanese adult patients and no study in Japanese pediatric patients. Therefore, we need to continue collecting data to ensure efficacy, especially in Japan. The objectives of this study were to evaluate the exposure and efficacy of CPX-351 in adult and pediatric Japanese patients. For these purposes, population pharmacokinetic and exposure-response analysis was conducted based on the established model/analysis using non-Japanese data by incorporating the newly obtained results of a Japanese clinical trial. No significant differences in pharmacokinetic exposure and efficacy were observed between non-Japanese adult patients and Japanese adult or pediatric patients. This information supports CPX-351 as a treatment option for untreated Japanese t-AML/AML-MRC patients on the basis of efficacy and safety when referred to the evidence from non-Japanese subjects.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"60 ","pages":"Article 101038"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892966","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

Development of intestinal organoids and microphysiological systems and their application to drug discovery

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2025-02-01 DOI: 10.1016/j.dmpk.2024.101045

Takahiro Iwao, Tamihide Matsunaga

{"title":"Development of intestinal organoids and microphysiological systems and their application to drug discovery","authors":"Takahiro Iwao, Tamihide Matsunaga","doi":"10.1016/j.dmpk.2024.101045","DOIUrl":"10.1016/j.dmpk.2024.101045","url":null,"abstract":"<div><div>The intestines are an important organ with a variety of functions. For drug discovery research, experimental animals and Caco-2 cells derived from a human colon carcinoma may be used to evaluate the absorption and safety of orally administered drugs. These systems have issues, such as species differences with humans in experimental animals, variations in gene expression patterns, very low drug-metabolizing activities in Caco-2 cells, and the recent trend toward reduced animal testing. Thus, there is a need for new evaluation systems. Intestinal organoid technology and microphysiological systems (MPS) have attracted attention as novel evaluation systems for predicting drug disposition, safety, and efficacy in humans in vitro. Intestinal organoids are three-dimensional structures that contain a variety of intestinal cells. They also contain crypt-villus structures similar to those of living bodies. Using MPS, it is possible to improve the functionality of cells and evaluate the linkage and crosstalk between the intestine and the liver. These systems are expected to be powerful tools for drug discovery research to predict efficacy and toxicity in humans. This review outlines the current status of intestinal organoids and MPS studies.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"60 ","pages":"Article 101045"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028108","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

Organoids and microphysiological systems for pharmaceutical research of viral respiratory infections

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2025-02-01 DOI: 10.1016/j.dmpk.2024.101041

Sayaka Deguchi , Fuki Yokoi , Kazuo Takayama

{"title":"Organoids and microphysiological systems for pharmaceutical research of viral respiratory infections","authors":"Sayaka Deguchi , Fuki Yokoi , Kazuo Takayama","doi":"10.1016/j.dmpk.2024.101041","DOIUrl":"10.1016/j.dmpk.2024.101041","url":null,"abstract":"<div><div>In the pharmaceutical research of viral respiratory infections, cell culture models have traditionally been used to evaluate the therapeutic effects of candidate compounds. Although cell lines are easy to handle and cost-effective, they do not fully replicate the characteristics of human respiratory organs. Recently, organoids and microphysiological systems (MPS) have been employed to overcome this limitation for <em>in vitro</em> testing of drugs against viral respiratory infections. Advanced disease modeling using organoids, self-organized three-dimensional (3D) cell culture models derived from stem cells, or MPS, models for culturing multiple cell types in a microfluidic device and capable of recapitulating a physiological 3D dynamic environment, can accurately replicate the complex functions of respiratory organs, thus making them valuable tools for elucidating the organ damages caused by viral respiratory infections and evaluating the efficacy of candidate drugs against them. Recently, a wide range of organoids and MPS have been developed to model the complex pathophysiology caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and assess therapeutic drugs. In this review, we evaluate the latest pharmaceutical research on coronavirus disease 2019 (COVID-19) that utilizes organoids and MPS and discuss future perspectives of their applications.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"60 ","pages":"Article 101041"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028183","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