Translational and Clinical Pharmacology最新文献_第3页

A review of the current state in neointimal hyperplasia development following endovascular intervention and minor emphasis on new horizons in immunotherapy. 回顾血管内介入术后新内膜增生的发展现状，并重点介绍免疫疗法的新前景。

IF 1.1

Translational and Clinical Pharmacology Pub Date : 2023-12-01 Epub Date: 2023-11-22 DOI: 10.12793/tcp.2023.31.e18

Rasit Dinc

{"title":"A review of the current state in neointimal hyperplasia development following endovascular intervention and minor emphasis on new horizons in immunotherapy.","authors":"Rasit Dinc","doi":"10.12793/tcp.2023.31.e18","DOIUrl":"10.12793/tcp.2023.31.e18","url":null,"abstract":"Endovascular strategies play a vital role in the treatment of peripheral arterial disease (PAD). However, luminal loss or restenosis after endovascular intervention remains a significant challenge. The main underlying mechanisms are negative vascular remodeling and elastic recoil in balloon angioplasty. During stenting, the main reason for this complex is neointimal proliferation. Endothelial cell injury due to endovascular intervention initiates a series of molecular events, such as overexpression of growth factors, cytokine secretion, and adhesion molecules. These induce platelet activation and inflammatory processes, which trigger the proliferation and migration of vascular smooth muscle cells into the intima, resulting in neointimal hyperplasia. During this process, PAD progression is mainly caused by chronic inflammation, in which macrophages play a central role. Of the current strategies, drug release interventions aim to suppress restenosis using antiproliferative drugs, such as sirolimus and paclitaxel, during drug release. These drugs inhibit vascular reendothelialization and reduce late in-stent restenosis. For this reason, immunotherapy can be considered an important alternative. Interventions that polarize macrophages to the M2 subtype are particularly important, as they shape the immune response in an anti-inflammatory direction and contribute to tissue repair. However, there are several challenges to overcome, such as localizing antiproliferative or polarizing agents only to areas of vascular injury. This review discusses, based on the early study observations, immunotherapeutic approaches to prevent restenosis after endovascular intervention for the treatment of PAD.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"31 4","pages":"191-201"},"PeriodicalIF":1.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10772059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetics of low doses of colchicine in the leukocytes of Japanese healthy individuals. 低剂量秋水仙碱在日本健康人白细胞中的药代动力学。

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2023-12-01 Epub Date: 2023-12-12 DOI: 10.12793/tcp.2023.31.e19

Akiko Mutoh, Hitoshi Uehara, Asano Maeda, Akihiro Tokushige, Yasushi Higashiuesato, Mika Maeda, Yuji Kumagai, Shinichiro Ueda

{"title":"Pharmacokinetics of low doses of colchicine in the leukocytes of Japanese healthy individuals.","authors":"Akiko Mutoh, Hitoshi Uehara, Asano Maeda, Akihiro Tokushige, Yasushi Higashiuesato, Mika Maeda, Yuji Kumagai, Shinichiro Ueda","doi":"10.12793/tcp.2023.31.e19","DOIUrl":"10.12793/tcp.2023.31.e19","url":null,"abstract":"The venerable drug colchicine has garnered significant recent attention due to its endorsement by the United States Food and Drug Administration as an anti-inflammatory medication for cardiovascular diseases. However, the administration of this drug at its minimal available dose of 0.5 mg has been associated with certain adverse reactions. Once colchicine is administered, the drug disappears from blood in a short time and distributes in the leukocytes for a certain period of time that elicits anti-inflammatory effect. Consequently, an in-depth comprehension of the pharmacokinetics of lower dosages within leukocytes assumes important for its broader application in routine clinical contexts. In this study, we present a comprehensive analysis of the pharmacological disposition of colchicine in the plasma, polymorphonuclear leukocytes, and mononuclear leukocytes among healthy Japanese male subjects, following both single and multiple oral administrations of 0.5 mg and 0.25 mg doses of colchicine. Our investigation reveals that colchicine persists within leukocyte populations even when administered at reduced dosages. The findings herein hold promise for mitigating the adverse effects associated with its use in the treatment of inflammatory cardiovascular disorders.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"31 4","pages":"217-225"},"PeriodicalIF":0.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10772056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adaptive design clinical trials: current status by disease and trial phase in various perspectives. 自适应设计临床试验：从不同角度看疾病和试验阶段的现状。

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2023-12-01 Epub Date: 2023-12-21 DOI: 10.12793/tcp.2023.31.e21

Hyunjoon Lee, Sejung Hwang, In-Jin Jang, Jae-Yong Chung, Jaeseong Oh

{"title":"Adaptive design clinical trials: current status by disease and trial phase in various perspectives.","authors":"Hyunjoon Lee, Sejung Hwang, In-Jin Jang, Jae-Yong Chung, Jaeseong Oh","doi":"10.12793/tcp.2023.31.e21","DOIUrl":"10.12793/tcp.2023.31.e21","url":null,"abstract":"An adaptive design is a clinical trial design that allows for modification of a structured plan in a clinical trial based on data accumulated during pre-planned interim analyses. This flexible approach to clinical trial design improves the success rate of clinical trials while reducing time, cost, and sample size compared to conventional methods. The purpose of this study is to identify the current status of adaptive design and present key considerations for planning an appropriate adaptive design based on specific circumstances. We searched for clinical trials conducted between January 2006 to July 2021 in the Clinical Trials Registry (ClinicalTrials.gov) using keywords specified in the Food and Drug Administration Adaptive Design Clinical Trial Guidelines. In order to analyze the adaptive designs used in selected cases, we classified the results according to the phase of the clinical trial, type of indication, and the specific adaptation method employed. A total of 267 clinical trials were identified on ClinicalTrials.gov. Among them, 236 clinical trials actually applied adaptive designs and were classified according to phase, indication types, and adaptation methods. Adaptive designs were most frequently used in phase 2 clinical trials and oncology research. The most commonly used adaptation method was the adaptive treatment selection design. In the case of coronavirus disease 2019, the most frequently used designs were adaptive platform design and seamless design. Through this study, we expect to provide valuable insights and considerations for the implementation of adaptive design clinical trials in different diseases and stages.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"31 4","pages":"202-216"},"PeriodicalIF":0.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10772057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetic properties of a new sustained-release pregabalin tablet in subjects with reduced renal function. 肾功能减退者服用新型普瑞巴林缓释片的药代动力学特性

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2023-12-01 Epub Date: 2023-12-20 DOI: 10.12793/tcp.2023.31.e20

Maria Park, Suein Choi, Sungpil Han, Wonsuk Shin, Anhye Kim, Seunghoon Han, Bomin Kim, Yeji Lim, Hyounggyoon Yoo

{"title":"Pharmacokinetic properties of a new sustained-release pregabalin tablet in subjects with reduced renal function.","authors":"Maria Park, Suein Choi, Sungpil Han, Wonsuk Shin, Anhye Kim, Seunghoon Han, Bomin Kim, Yeji Lim, Hyounggyoon Yoo","doi":"10.12793/tcp.2023.31.e20","DOIUrl":"10.12793/tcp.2023.31.e20","url":null,"abstract":"A new sustained-release (SR) pregabalin tablet, YHD1119, was formulated for once-daily dosing. In the current study, we aimed to evaluate the pharmacokinetics of YHD1119 tablets in patients with reduced renal function. Subjects were grouped by creatinine clearance: > 60 mL/min/1.73m2 (Cohort A) and 30-60 mL/min/1.73m2 (Cohort B). Eight subjects in Cohort A received a YHD1119 75 mg tablet (Y75T) and a YHD1119 150 mg tablet (Y150T) in each period, and eight subjects in Cohort B received a Y75T. Non-compartment analysis and population pharmacokinetic analysis using a one-compartment model with first-order elimination and first-order absorption with lag time were performed. Sixteen subjects completed the study. The geometric mean ratio (GMR) (90% confidence intervals [CI]) for maximum concentration (Cmax), and area under the concentration-time profile from 0 to the last measurable time (AUClast) after Y75T of Cohort B to those of Y75T of Cohort A were 1.2273 (1.0245-1.4701), and 2.4146 (1.8142-3.2138), respectively. The GMR (90% CI) for Cmax, and AUClast after Y75T of Cohort B to those of Y150T of Cohort A were 0.6476 (0.5229-0.8021), and 1.1471 (0.8418-1.5632), respectively. Simulated steady-steady pregabalin concentrations after once-daily Y75T dosing in subjects with eGFR 45 mL/min/1.73 m2 were within the range of steady-state concentrations simulated after once-daily Y150T dosing in subjects with eGFR 90 mL/min/1.73 m2. The total pregabalin exposure of Y75T in patients with moderate renal impairment was comparable with that of Y150T in subjects with near-normal renal function.Trial registration: ClinicalTrials.gov Identifier: NCT05012436.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"31 4","pages":"226-237"},"PeriodicalIF":0.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10772055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phage-host-immune system dynamics in bacteriophage therapy: basic principles and mathematical models. 噬菌体疗法中的噬菌体-宿主-免疫系统动力学：基本原理和数学模型。

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2023-12-01 Epub Date: 2023-11-22 DOI: 10.12793/tcp.2023.31.e17

Dongwoo Chae

{"title":"Phage-host-immune system dynamics in bacteriophage therapy: basic principles and mathematical models.","authors":"Dongwoo Chae","doi":"10.12793/tcp.2023.31.e17","DOIUrl":"10.12793/tcp.2023.31.e17","url":null,"abstract":"Phage therapy is progressively being recognized as a viable alternative to conventional antibiotic treatments, particularly in the context of multi-drug resistant bacterial challenges. However, the intricacies of the pharmacokinetics and pharmacodynamics (PKPD) pertaining to phages remain inadequately elucidated. A salient characteristic of phage PKPD is the inherent ability of phages to undergo replication. In this review, I proffer mathematical models that delineate the intricate dynamics encompassing the phage, the host organism, and the immune system. Fundamental tenets associated with proliferative and inundation thresholds are explored, and distinctions between active and passive therapies are accentuated. Furthermore, I present models that aim to illuminate the multifaceted interactions amongst diverse phage strains and bacterial subpopulations, each possessing distinct sensitivities to phages. The synergistic relationship between phages and the immune system is critically examined, demonstrating how the host's immunological function can influence the requisite phage dose for an optimal therapeutic outcome. A profound understanding of the presented modeling methodologies is paramount for researchers in the realms of clinical pharmacology and PKPD modeling interested in phage therapy. Such insights facilitate a more nuanced interpretation of dose-response relationships, enable the selection of potent phages, and aid in the optimization of phage cocktails.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"31 4","pages":"167-190"},"PeriodicalIF":0.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10772058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transforming clinical trials: the emerging roles of large language models. 转变临床试验：大型语言模型的新兴作用。

IF 1.1

Translational and Clinical Pharmacology Pub Date : 2023-09-01 Epub Date: 2023-09-19 DOI: 10.12793/tcp.2023.31.e16

Jong-Lyul Ghim, Sangzin Ahn

引用次数: 0

Response surface analyses of antihypertensive effects of angiotensin receptor blockers and amlodipine or hydrochlorothiazide combination therapy in patients with essential hypertension. 血管紧张素受体阻滞剂与氨氯地平或氢氯噻嗪联合治疗原发性高血压患者降压作用的响应面分析。

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2023-09-01 Epub Date: 2023-09-19 DOI: 10.12793/tcp.2023.31.e15

Minhee Cho, Eunsook Oh, Byungjin Ahn, MoonTae Yoon

{"title":"Response surface analyses of antihypertensive effects of angiotensin receptor blockers and amlodipine or hydrochlorothiazide combination therapy in patients with essential hypertension.","authors":"Minhee Cho, Eunsook Oh, Byungjin Ahn, MoonTae Yoon","doi":"10.12793/tcp.2023.31.e15","DOIUrl":"10.12793/tcp.2023.31.e15","url":null,"abstract":"While previous studies have examined the dose-response characteristics of certain antihypertensive drugs alone or in combination, response surface analysis for combination therapies involving angiotensin receptor blockers (ARBs) and either amlodipine (AML) or hydrochlorothiazide (HCT) has not been explored, particularly in the context of low-dose combinations. The objectives of present study were to generate useful dose-response information for the combination of ARB/AML or ARB/HCT and to predict the blood pressure lowering effects of combination therapies compared to monotherapies. We reviewed the New Drug Application data of combination drugs of ARB/AML and ARB/HCT. Data on systolic blood pressure (SBP), from studies conducted using a factorial dose-response design over a period of 8-12 weeks, were used. The placebo-subtracted SBP change was used for analysis. Response surface analyses of the collected data were conducted using a polynomial regression model. For ARB/AML combination, the quadratic polynomial regression model containing two linear terms, two quadratic terms, and one interaction term was best fitted to the naïve pooled data. Meanwhile, for ARB/HCT combination, the best-fitted model was a quadratic model that included two linear terms and two quadratic terms. The 1/2-dose combination of these medications, compared to each monotherapy, resulted in predicted SBP reductions that were 8-30% greater. The ratio of the estimated antihypertensive effects of the combination to the expected additive effects of each component ranged from 82% to 100% of the expected effect. These results can provide a rationale for developing lower-dose combinations of ARB/AML or ARB/HCT and assist in designing clinical trials.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"31 3","pages":"154-166"},"PeriodicalIF":0.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e5/9d/tcp-31-154.PMC10551747.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41141031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of rifampin coadministration on the pharmacokinetics of digoxin: a real-world data approach. 利福平联合用药对地高辛药代动力学的影响：一种真实世界的数据方法。

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2023-09-01 Epub Date: 2023-09-08 DOI: 10.12793/tcp.2023.31.e13

JungJin Oh, Byungwook Kim, SeungHwan Lee

引用次数: 0

Quantification of OATP1B1 endogenous metabolites coproporphyrin I and III in human urine. 人类尿液中OATP1B1内源性代谢物粪卟啉I和III的定量。

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2023-09-01 Epub Date: 2023-08-23 DOI: 10.12793/tcp.2023.31.e12

Yeonseo Jang, Jihyun Kang, Sejung Hwang, Jae-Yong Chung, Joo-Youn Cho

{"title":"Quantification of OATP1B1 endogenous metabolites coproporphyrin I and III in human urine.","authors":"Yeonseo Jang, Jihyun Kang, Sejung Hwang, Jae-Yong Chung, Joo-Youn Cho","doi":"10.12793/tcp.2023.31.e12","DOIUrl":"10.12793/tcp.2023.31.e12","url":null,"abstract":"Coproporphyrin (CP)-I and CP-III are the markers of organic anion-transporting polypeptides' (OATPs) activities, and they are porphyrin metabolites that originate from heme synthesis. Furthermore, CP-I and CP-III, which are OATP1B endogenous metabolites, have gradually attracted the attention of scientists and researchers in recent years. Previous studies have also observed CP-I and CP-III levels as clinical biomarkers for predicting OATP1B inhibition in drug-drug interaction studies. To establish an accurate ultra-high performance liquid chromatography-mass spectrometry method for the quantitation of CP-I and CP-III, we reviewed previous methodological publications and applied them to a clinical pharmacology study using a human urine matrix. We used 13.25 M formic acid as a working solution for internal standards (CP-I 15N4 and CP-III d8) to avoid isobaric interference. The calibration curve showed good linearity in the range of 1-100 ng/mL, with a correlation coefficient (R2) higher than 0.996 in each validation batch. Both the between-run and within-run assays achieved good precision and accuracy, and we found that both CP-I and CP-III were stable in the pre-study validation. The method exhibited suitable dilution integrity, allowing for the re-analysis of samples with concentrations exceeding the upper limit of quantification through dilution. Overall, the application of the described method in a clinical study revealed that it can be utilized effectively to monitor drug-drug interactions mediated by OATP1B.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"31 3","pages":"139-147"},"PeriodicalIF":0.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/65/46/tcp-31-139.PMC10551744.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41155409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

What goes in the regulatory clinical pharmacology package for an oncolytic virus? 溶瘤病毒的监管临床药理学包里有什么？

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2023-09-01 Epub Date: 2023-09-13 DOI: 10.12793/tcp.2023.31.e14

Sun Young Yum, Kyungho Jang, Francine Attié de Castro, Amandine Manon

引用次数: 0