Drug Metabolism and Pharmacokinetics最新文献_第2页

Organoids and microphysiological systems for pharmaceutical research of viral respiratory infections.

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-11-15 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":"https://doi.org/10.1016/j.dmpk.2024.101041","url":null,"abstract":"<p><p>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 in vitro 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.</p>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"60 ","pages":"101041"},"PeriodicalIF":2.7,"publicationDate":"2024-11-15","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":"","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 : 2024-11-09 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

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 : 2024-11-07 DOI: 10.1016/j.dmpk.2024.101036

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

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 : 2024-11-05 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":"https://doi.org/10.1016/j.dmpk.2024.101035","url":null,"abstract":"<p><p>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 (fa/fa) rats as an obese model and Zucker (+/+) rats as a control. No difference in systemic clearance (CL<sub>tot</sub>) after intravenous administration was observed between the two groups. However, transdermal bioavailability (F) and fentanyl release ratio from the formulation (F<sub>a</sub>) were significantly increased in Zucker (fa/fa) rats compared to Zucker (+/+) rats. Skin availability (F<sub>skin</sub>), calculated as F divided by F<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.</p>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"60 ","pages":"101035"},"PeriodicalIF":2.7,"publicationDate":"2024-11-05","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of plasma vonoprazan and CYP3A activity using its endogenous marker and genetic variants in patients with digestive system disorders 利用消化系统疾病患者的内源性标记物和遗传变异分析血浆中伏诺派赞和 CYP3A 活性的特征

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-10-01 DOI: 10.1016/j.dmpk.2024.101027

Kenta Sakaguchi , Takafumi Naito , Kohei Hoshikawa , Yukari Miyadera , Hironari Tanaka , Emi Nakatsugawa , Takahisa Furuta , Ken Sugimoto , Junichi Kawakami

{"title":"Characterization of plasma vonoprazan and CYP3A activity using its endogenous marker and genetic variants in patients with digestive system disorders","authors":"Kenta Sakaguchi , Takafumi Naito , Kohei Hoshikawa , Yukari Miyadera , Hironari Tanaka , Emi Nakatsugawa , Takahisa Furuta , Ken Sugimoto , Junichi Kawakami","doi":"10.1016/j.dmpk.2024.101027","DOIUrl":"10.1016/j.dmpk.2024.101027","url":null,"abstract":"<div><div>Factors that determine clinical responses to vonoprazan remain unknown. This study aimed to characterize plasma vonoprazan and CYP3A activity using its endogenous marker and genetic variants in patients with digestive system disorders. Fifty-three patients who were receiving vonoprazan for at least 3 days were enrolled. Blood samples for determination of plasma vonoprazan and its metabolite (ODA-VP) were obtained. Plasma 4β-hydroxycholesterol (4β-OHC), CYP3A5 and ABCB1 genotypes, and plasma gastrin were determined. CYP3A recognition for vonoprazan was evaluated using recombinant CYP3A proteins. Plasma vonoprazan levels exhibited a large interindividual variation. The absolute plasma concentration of vonoprazan was correlated with its dose-normalized value, and had a positive correlation with the inverse value of its metabolic ratio. A negative correlation was observed between plasma vonoprazan and 4β-OHC levels. The metabolic ratio of vonoprazan was positively correlated with the plasma 4β-OHC level. Genetic variants of CYP3A5 and ABCB1 were not associated with the plasma concentration of vonoprazan and its metabolic ratio. Possible saturated metabolism of vonoprazan to its major metabolite was observed at a therapeutic dose. Although the CYP3A5 genotype did not alter plasma vonoprazan, CYP3A activity based on plasma 4β-OHC partially explained the variation in plasma vonoprazan in patients with digestive system disorders.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"58 ","pages":"Article 101027"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141707033","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

Understanding mechanisms of negative food effect for voclosporin using physiologically based pharmacokinetic modeling 利用基于生理学的药代动力学模型了解voclosporin的负食物效应机制。

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-09-10 DOI: 10.1016/j.dmpk.2024.101032

Ayahisa Watanabe, Takanori Akazawa, Motohiro Fujiu

{"title":"Understanding mechanisms of negative food effect for voclosporin using physiologically based pharmacokinetic modeling","authors":"Ayahisa Watanabe, Takanori Akazawa, Motohiro Fujiu","doi":"10.1016/j.dmpk.2024.101032","DOIUrl":"10.1016/j.dmpk.2024.101032","url":null,"abstract":"<div><div>Negative food effect refers to a reduction in bioavailability, when a drug is taken with food. Voclosporin, a highly lipophilic cyclic peptide drug for treatment of active lupus nephritis, has shown negative food effect in clinical trials. Here, the cause of the negative food effect of voclosporin was investigated using physiologically based pharmacokinetic (PBPK) modeling to understand the mechanism responsible for oral absorption of voclosporin. Voclosporin is a substrate for P-glycoprotein and CYP3A4, and it has been evaluated for intestinal membrane permeability in human induced pluripotent stem cell-derived intestinal epithelial cells (hiPSC-IECs). The membrane permeability in hiPSC-IECs is integrated into the PBPK model for simulating permeability accurately. The PBPK model simulated the systemic PK profile in fasted state in human. Then, the PBPK model with <em>in vitro</em> adsorption of voclosporin onto food simulated the systemic PK profile in fed state for food effect. In addition, the PBPK model for rats also simulated the plasma profile of voclosporin for the food effect. These results suggest that a possible cause of the negative food effect of voclosporin is the adsorption of voclosporin to food in gastrointestinal tract. These approaches could facilitate understanding of the mechanisms responsible for oral absorption of cyclic peptides.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"59 ","pages":"Article 101032"},"PeriodicalIF":2.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460449","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

Quantitative prediction of CYP3A induction-mediated drug-drug interactions in clinical practice 定量预测临床实践中 CYP3A 诱导的药物间相互作用

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-08-01 DOI: 10.1016/j.dmpk.2024.101010

{"title":"Quantitative prediction of CYP3A induction-mediated drug-drug interactions in clinical practice","authors":"","doi":"10.1016/j.dmpk.2024.101010","DOIUrl":"10.1016/j.dmpk.2024.101010","url":null,"abstract":"<div><p>There have been no reports on the quantitative prediction of CYP3A induction-mediated decreases in AUC and <em>C</em><sub>max</sub> for drug candidates identified as a “victims” of CYP3A induction. Our previous study separately evaluated the fold-induction of hepatic and intestinal CYP3A by known inducers using clinical induction data and revealed that we were able to quantitatively predict the AUC ratio (AUCR) of a few CYP3A substrates in the presence and absence of CYP3A inducers. In the present study, we investigate the predictability of AUCR and also <em>C</em><sub>max</sub> ratio (C<sub>max</sub>R) in additional 54 clinical studies. The fraction metabolized by CYP3A (<em>f</em><sub>m</sub>), the intestinal bioavailability (<em>F</em><sub>g</sub>), and the hepatic intrinsic clearance (<em>CL</em><sub>int</sub>) of substrates were determined by the in vitro experiments as well as clinical data used for calculating AUCR and C<sub>max</sub>R. The result showed that 65–69% and 65–67% of predictions were within 2-fold of observed AUCR and C<sub>max</sub>R, respectively. A simulation using multiple parameter combinations suggested that the variability of <em>f</em><sub>m</sub> and <em>F</em><sub>g</sub> within a certain range might have a minimal impact on the calculation output. These findings suggest that clinical AUCR and C<sub>max</sub>R of CYP3A substrates can be quantitatively predicted from the preclinical stage.</p></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"57 ","pages":"Article 101010"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347436724000168/pdfft?md5=05af9e2101d932059de43ff8740db672&pid=1-s2.0-S1347436724000168-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140147294","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

Genetic variation present in the CYP3A4 gene in Ni-Vanuatu and Kenyan populations in malaria endemicity 疟疾流行地区尼-瓦努阿图和肯尼亚人口中 CYP3A4 基因的遗传变异

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-08-01 DOI: 10.1016/j.dmpk.2024.101029

Kelvin Musyoka , Chim W. Chan , Evelyn Marie Gutiérrez Rico , Protus Omondi , Caroline Kijogi , Takatsugu Okai , James Kongere , Mtakai Ngara , Wataru Kagaya , Bernard N. Kanoi , Masahiro Hiratsuka , Yasutoshi Kido , Jesse Gitaka , Akira Kaneko

{"title":"Genetic variation present in the CYP3A4 gene in Ni-Vanuatu and Kenyan populations in malaria endemicity","authors":"Kelvin Musyoka , Chim W. Chan , Evelyn Marie Gutiérrez Rico , Protus Omondi , Caroline Kijogi , Takatsugu Okai , James Kongere , Mtakai Ngara , Wataru Kagaya , Bernard N. Kanoi , Masahiro Hiratsuka , Yasutoshi Kido , Jesse Gitaka , Akira Kaneko","doi":"10.1016/j.dmpk.2024.101029","DOIUrl":"10.1016/j.dmpk.2024.101029","url":null,"abstract":"<div><p>Cytochrome P450 3A4 (CYP3A4) enzyme is involved in the metabolism of about 30 % of clinically used drugs, including the antimalarials artemether and lumefantrine. <em>CYP3A4</em> polymorphisms yield enzymatic variants that contribute to inter-individual variation in drug metabolism. Here, we examined <em>CYP3A4</em> polymorphisms in populations from malaria-endemic islands in Lake Victoria, Kenya, and Vanuatu, to expand on the limited data sets. We used archived dried blood spots collected from 142 Kenyan and 263 ni-Vanuatu adults during cross-sectional malaria surveys in 2013 and 2005–13, respectively, to detect <em>CYP3A4</em> variation by polymerase chain reaction (PCR) and sequencing. In Kenya, we identified 14 <em>CYP3A4</em> single nucleotide polymorphisms (SNPs), including the 4713G (<em>CYP3A4∗1B</em>; allele frequency 83.9 %) and 19382A (<em>CYP3A4∗15</em>; 0.7 %) variants that were previously linked to altered metabolism of antimalarials. In Vanuatu, we detected 15 SNPs, including the 4713A (<em>CYP3A4∗1A</em>; 88.6 %) and 25183C (<em>CYP3A4∗18</em>; 0.6 %) variants. Additionally, we detected a rare and novel SNP C4614T (0.8 %) in the 5′ untranslated region. A higher proportion of <em>CYP3A4</em> genetic variance was found among ni-Vanuatu populations (16 %) than among Lake Victoria Kenyan populations (8 %). Our work augments the scarce data sets and contributes to improved precision medicine approaches, particularly to anti-malarial chemotherapy, in East African and Pacific Islander populations.</p></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"57 ","pages":"Article 101029"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347436724000351/pdfft?md5=e58051588ccdc0e46f04f97fd0bf3ea1&pid=1-s2.0-S1347436724000351-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141843365","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

Physiologically based pharmacokinetic modeling of CYP2C8 substrate rosiglitazone and its metabolite to predict metabolic drug-drug interaction 基于生理学的 CYP2C8 底物罗格列酮及其代谢物的药代动力学模型，以预测代谢药物与药物之间的相互作用。

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-08-01 DOI: 10.1016/j.dmpk.2024.101023

Nilesh Gaud , Dawid Gogola , Anna Kowal-Chwast , Ewelina Gabor-Worwa , Peter Littlewood , Krzysztof Brzózka , Kamil Kus , Maria Walczak

{"title":"Physiologically based pharmacokinetic modeling of CYP2C8 substrate rosiglitazone and its metabolite to predict metabolic drug-drug interaction","authors":"Nilesh Gaud , Dawid Gogola , Anna Kowal-Chwast , Ewelina Gabor-Worwa , Peter Littlewood , Krzysztof Brzózka , Kamil Kus , Maria Walczak","doi":"10.1016/j.dmpk.2024.101023","DOIUrl":"10.1016/j.dmpk.2024.101023","url":null,"abstract":"<div><p>Rosiglitazone is an activator of nuclear peroxisome proliferator-activated (PPAR) receptor gamma used in the treatment of type 2 diabetes mellitus. The elimination of rosiglitazone occurs mainly via metabolism, with major contribution by enzyme cytochrome P450 (CYP) 2C8. Primary routes of rosiglitazone metabolism are N-demethylation and hydroxylation. Modulation of CYP2C8 activity by co-administered drugs lead to prominent changes in the exposure of rosiglitazone and its metabolites. Here, we attempt to develop mechanistic parent-metabolite physiologically based pharmacokinetic (PBPK) model for rosiglitazone. Our goal is to predict potential drug-drug interaction (DDI) and consequent changes in metabolite N-desmethyl rosiglitazone exposure. The PBPK modeling was performed in the PKSim® software using clinical pharmacokinetics data from literature. The contribution to N-desmethyl rosiglitazone formation by CYP2C8 was delineated using vitro metabolite formation rates from recombinant enzyme system. Developed model was verified for prediction of rosiglitazone DDI potential and its metabolite exposure based on observed clinical DDI studies. Developed model exhibited good predictive performance both for rosiglitazone and N-desmethyl rosiglitazone respectively, evaluated based on commonly acceptable criteria. In conclusion, developed model helps with prediction of CYP2C8 DDI using rosiglitazone as a substrate, as well as changes in metabolite exposure. In vitro data for metabolite formation can be successfully utilized to translate to in vivo conditions.</p></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"57 ","pages":"Article 101023"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874459","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

Iminium ion metabolites are formed from nintedanib by human CYP3A4 人类 CYP3A4 可从 nintedanib 生成氨离子代谢物

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2024-08-01 DOI: 10.1016/j.dmpk.2024.101025

{"title":"Iminium ion metabolites are formed from nintedanib by human CYP3A4","authors":"","doi":"10.1016/j.dmpk.2024.101025","DOIUrl":"10.1016/j.dmpk.2024.101025","url":null,"abstract":"<div><p>Nintedanib is used to treat idiopathic pulmonary fibrosis, systemic sclerosis, interstitial lung disease, and progressive fibrotic interstitial lung disease. It is primarily cleared via hepatic metabolism, hydrolysis, and glucuronidation. In addition, formation of the iminium ion, a possible reactive metabolite, was predicted based on the chemical structure of nintedanib. To obtain a hint which may help to clarify the cause of nintedanib-induced liver injury, we investigated whether iminium ions were formed in the human liver. To detect unstable iminium ions using liquid chromatography-tandem mass spectrometry (LC-MS/MS), potassium cyanide was added to the reaction mixture as a trapping agent. Human liver and intestinal microsomes were incubated with nintedanib in the presence of NADPH to form two iminium ion metabolites on the piperazine ring. Their formation is strongly inhibited by ketoconazole, a potent cytochrome P450 (CYP) 3A4 inhibitor. Among the recombinant P450s, only CYP3A4 formed cyanide adducts. The role of CYP3A4 was supported by the positive correlation between CYP3A4 protein abundance, as determined by LC-MS-based proteomics, and the formation of cyanide adducts in 25 individual human liver microsomes. In conclusion, we have demonstrated that iminium ion metabolites are formed from nintedanib by CYP3A4 as potential reactive metabolites.</p></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"57 ","pages":"Article 101025"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141396519","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