Journal of Pharmacokinetics and Pharmacodynamics最新文献_第7页

Go beyond the limits of genetic algorithm in daily covariate selection practice. 在日常协变量选择实践中超越遗传算法的极限。

IF 2.2 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-04-01 Epub Date: 2023-07-26 DOI: 10.1007/s10928-023-09875-7

D Ronchi, E M Tosca, R Bartolucci, P Magni

{"title":"Go beyond the limits of genetic algorithm in daily covariate selection practice.","authors":"D Ronchi, E M Tosca, R Bartolucci, P Magni","doi":"10.1007/s10928-023-09875-7","DOIUrl":"10.1007/s10928-023-09875-7","url":null,"abstract":"Covariate identification is an important step in the development of a population pharmacokinetic/pharmacodynamic model. Among the different available approaches, the stepwise covariate model (SCM) is the most used. However, SCM is based on a local search strategy, in which the model-building process iteratively tests the addition or elimination of a single covariate at a time given all the others. This introduces a heuristic to limit the searching space and then the computational complexity, but, at the same time, can lead to a suboptimal solution. The application of genetic algorithms (GAs) for covariate selection has been proposed as a possible solution to overcome these limitations. However, their actual use during model building is limited by the extremely high computational costs and convergence issues, both related to the number of models being tested. In this paper, we proposed a new GA for covariate selection to address these challenges. The GA was first developed on a simulated case study where the heuristics introduced to overcome the limitations affecting currently available GA approaches resulted able to limit the selection of redundant covariates, increase replicability of results and reduce convergence times. Then, we tested the proposed GA on a real-world problem related to remifentanil. It obtained good results both in terms of selected covariates and fitness optimization, outperforming the SCM.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":" ","pages":"109-121"},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9925237","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

Low-dimensional neural ODEs and their application in pharmacokinetics. 低维神经ODEs及其在药代动力学中的应用。

IF 2.2 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-04-01 Epub Date: 2023-10-14 DOI: 10.1007/s10928-023-09886-4

Dominic Stefan Bräm, Uri Nahum, Johannes Schropp, Marc Pfister, Gilbert Koch

{"title":"Low-dimensional neural ODEs and their application in pharmacokinetics.","authors":"Dominic Stefan Bräm, Uri Nahum, Johannes Schropp, Marc Pfister, Gilbert Koch","doi":"10.1007/s10928-023-09886-4","DOIUrl":"10.1007/s10928-023-09886-4","url":null,"abstract":"Machine Learning (ML) is a fast-evolving field, integrated in many of today's scientific disciplines. With the recent development of neural ordinary differential equations (NODEs), ML provides a new tool to model dynamical systems in the field of pharmacology and pharmacometrics, such as pharmacokinetics (PK) or pharmacodynamics. The novel and conceptionally different approach of NODEs compared to classical PK modeling creates challenges but also provides opportunities for its application. In this manuscript, we introduce the functionality of NODEs and develop specific low-dimensional NODE structures based on PK principles. We discuss two challenges of NODEs, overfitting and extrapolation to unseen data, and provide practical solutions to these problems. We illustrate concept and application of our proposed low-dimensional NODE approach with several PK modeling examples, including multi-compartmental, target-mediated drug disposition, and delayed absorption behavior. In all investigated scenarios, the NODEs were able to describe the data well and simulate data for new subjects within the observed dosing range. Finally, we briefly demonstrate how NODEs can be combined with mechanistic models. This research work enhances understanding of how NODEs can be applied in PK analyses and illustrates the potential for NODEs in the field of pharmacology and pharmacometrics.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":" ","pages":"123-140"},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41203855","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

Evaluation of prompt engineering strategies for pharmacokinetic data analysis with the ChatGPT large language model. 用ChatGPT大型语言模型评估药代动力学数据分析的即时工程策略。

IF 2.2 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-04-01 Epub Date: 2023-11-11 DOI: 10.1007/s10928-023-09892-6

Euibeom Shin, Murali Ramanathan

{"title":"Evaluation of prompt engineering strategies for pharmacokinetic data analysis with the ChatGPT large language model.","authors":"Euibeom Shin, Murali Ramanathan","doi":"10.1007/s10928-023-09892-6","DOIUrl":"10.1007/s10928-023-09892-6","url":null,"abstract":"To systematically assess the ChatGPT large language model on diverse tasks relevant to pharmacokinetic data analysis. ChatGPT was evaluated with prototypical tasks related to report writing, code generation, non-compartmental analysis, and pharmacokinetic word problems. The writing task consisted of writing an introduction for this paper from a draft title. The coding tasks consisted of generating R code for semi-logarithmic graphing of concentration-time profiles and calculating area under the curve and area under the moment curve from time zero to infinity. Pharmacokinetics word problems on single intravenous, extravascular bolus, and multiple dosing were taken from a pharmacokinetics textbook. Chain-of-thought and problem separation were assessed as prompt engineering strategies when errors occurred. ChatGPT showed satisfactory performance on the report writing, code generation tasks and provided accurate information on the principles and methods underlying pharmacokinetic data analysis. However, ChatGPT had high error rates in numerical calculations involving exponential functions. The outputs generated by ChatGPT were not reproducible: the precise content of the output was variable albeit not necessarily erroneous for different instances of the same prompt. Incorporation of prompt engineering strategies reduced but did not eliminate errors in numerical calculations. ChatGPT has the potential to become a powerful productivity tool for writing, knowledge encapsulation, and coding tasks in pharmacokinetic data analysis. The poor accuracy of ChatGPT in numerical calculations require resolution before it can be reliably used for PK and pharmacometrics data analysis.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":" ","pages":"101-108"},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89718726","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

Explaining in-vitro to in-vivo efficacy correlations in oncology pre-clinical development via a semi-mechanistic mathematical model. 通过半机械数学模型解释肿瘤学临床前发展中体外与体内疗效的相关性。

IF 2.2 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-04-01 Epub Date: 2023-11-06 DOI: 10.1007/s10928-023-09891-7

Heinrich J Huber, Hitesh B Mistry

{"title":"Explaining in-vitro to in-vivo efficacy correlations in oncology pre-clinical development via a semi-mechanistic mathematical model.","authors":"Heinrich J Huber, Hitesh B Mistry","doi":"10.1007/s10928-023-09891-7","DOIUrl":"10.1007/s10928-023-09891-7","url":null,"abstract":"In-vitro to in-vivo correlations (IVIVC), relating in-vitro parameters like IC50 to in-vivo drug exposure in plasma and tumour growth, are widely used in oncology for experimental design and dose decisions. However, they lack a deeper understanding of the underlying mechanisms. Our paper therefore focuses on linking empirical IVIVC relations for small-molecule kinase inhibitors with a semi-mechanistic tumour-growth model. We develop an approach incorporating parameters like the compound's peak-trough ratio (PTR), Hill coefficient of in-vitro dose-response curves, and xenograft-specific properties. This leads to formulas for determining efficacious doses for tumor stasis under linear pharmacokinetics equivalent to traditional empirical IVIVC relations, but enabling more systematic analysis. Our findings reveal that in-vivo xenograft-specific parameters, specifically the growth rate (g) and decay rate (d), along with the average exposure, are generally more significant determinants of tumor stasis and effective dose than the compound's peak-trough ratio. However, as the Hill coefficient increases, the dependency of tumor stasis on the PTR becomes more pronounced, indicating that the compound is more influenced by its maximum or trough values rather than the average exposure. Furthermore, we discuss the translation of our method to predict population dose ranges in clinical studies and propose a resistance mechanism that solely relies on specific in-vivo xenograft parameters instead of IC50 exposure coverage. In summary, our study aims to provide a more mechanistic understanding of IVIVC relations, emphasizing the importance of xenograft-specific parameters and PTR on tumor stasis.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":" ","pages":"169-185"},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482795","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 pharmacokinetics and pharmacodynamics of efmarodocokin alfa (IL-22Fc). efmarodookin alfa（IL-22Fc）的群体药代动力学和药效学。

IF 2.2 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-04-01 Epub Date: 2023-10-20 DOI: 10.1007/s10928-023-09888-2

Yanke Yu, Michael E Rothenberg, Han Ting Ding, Ari Brekkan, Gizette Sperinde, Brandon Harder, Rong Zhang, Ryan Owen, Nastya Kassir, Annemarie N Lekkerkerker

{"title":"Population pharmacokinetics and pharmacodynamics of efmarodocokin alfa (IL-22Fc).","authors":"Yanke Yu, Michael E Rothenberg, Han Ting Ding, Ari Brekkan, Gizette Sperinde, Brandon Harder, Rong Zhang, Ryan Owen, Nastya Kassir, Annemarie N Lekkerkerker","doi":"10.1007/s10928-023-09888-2","DOIUrl":"10.1007/s10928-023-09888-2","url":null,"abstract":"Efmarodocokin alfa (IL-22Fc) is a fusion protein of human IL-22 linked to the crystallizable fragment (Fc) of human IgG4. It has been tested in multiple indications including inflammatory bowel disease (IBD). The purposes of the present analyses were to describe the population pharmacokinetics (PK) of efmarodocokin alfa and perform pharmacodynamic (PD) analysis on the longitudinal changes of the PD biomarker REG3A after efmarodocokin alfa treatment as well as identify covariates that affect efmarodocokin alfa PK and REG3A PD. The data used for this analysis included 182 subjects treated with efmarodocokin alfa in two clinical studies. The population PK and PD analyses were conducted sequentially. Efmarodocokin alfa concentration-time data were analyzed using a nonlinear mixed-effects modeling approach, and an indirect response model was adopted to describe the REG3A PD data with efmarodocokin alfa serum concentration linked to the increase in REG3A. The analysis software used were NONMEM and R. A 3-compartment model with linear elimination best described the PK of efmarodocokin alfa. The estimated population-typical value for clearance (CL) was 1.12 L/day, and volume of central compartment was 6.15 L. Efmarodocokin alfa CL increased with higher baseline body weight, C-reactive protein, and CL was 27.6% higher in IBD patients compared to healthy subjects. The indirect response PD model adequately described the longitudinal changes of REG3A after efmarodocokin alfa treatment. A popPK and PD model for efmarodocokin alfa and REG3A was developed and covariates affecting the PK and PD were identified.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":" ","pages":"141-153"},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49678761","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

Longitudinal modeling of efficacy response in patients with lupus nephritis receiving belimumab 接受贝利木单抗治疗的狼疮性肾炎患者疗效反应纵向模型

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-03-29 DOI: 10.1007/s10928-024-09907-w

{"title":"Longitudinal modeling of efficacy response in patients with lupus nephritis receiving belimumab","authors":"","doi":"10.1007/s10928-024-09907-w","DOIUrl":"https://doi.org/10.1007/s10928-024-09907-w","url":null,"abstract":"<h3>Abstract</h3> Belimumab was approved for active lupus nephritis (LN) in adults in the European Union and patients ≥ 5 years of age in the USA based on a Phase 3, double-blind, placebo-controlled, 104-week study. The study evaluated the efficacy of belimumab plus background standard therapy in adults with active LN using an intravenous (IV) dose of 10 mg/kg. A longitudinal analysis of Primary Efficacy Renal Response (PERR) and Complete Renal Response (CRR) was performed to assess whether patients with high proteinuria at the start of belimumab treatment would benefit from a higher dose. Responder probability was modeled as a logistic regression with probability a function of time and treatment (belimumab or placebo). Dropout risk at each visit was incorporated into a joint model of efficacy response; only efficacy data prior to dropout events (belimumab discontinuation, treatment failure, or withdrawal) were included. Average belimumab concentration over the first 4 and 12 weeks and baseline proteinuria were considered as continuous covariates. In general, renal response (PERR and CRR) over time was higher in patients receiving belimumab than in those receiving placebo. Baseline proteinuria was considered the most relevant predictor of renal response, with reduced efficacy in patients with increased proteinuria for both belimumab or placebo treatment. For belimumab-treated patients, belimumab exposure was not found to be an important predictor of renal response. In conclusion, the 10 mg/kg IV dose was considered appropriate in all patients and there was no evidence to suggest a higher response would be achieved by increasing the dose.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"53 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140323842","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

Employing zero-inflated beta distribution in an exposure-response analysis of TYK2/JAK1 inhibitor brepocitinib in patients with plaque psoriasis 在对斑块状银屑病患者使用 TYK2/JAK1 抑制剂 brepocitinib 进行暴露-反应分析时采用零膨胀贝塔分布

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-03-03 DOI: 10.1007/s10928-024-09901-2

Nikolaos Tsamandouras, Ruolun Qiu, Jim H. Hughes, Kevin Sweeney, John P. Prybylski, Christopher Banfield, Timothy Nicholas

{"title":"Employing zero-inflated beta distribution in an exposure-response analysis of TYK2/JAK1 inhibitor brepocitinib in patients with plaque psoriasis","authors":"Nikolaos Tsamandouras, Ruolun Qiu, Jim H. Hughes, Kevin Sweeney, John P. Prybylski, Christopher Banfield, Timothy Nicholas","doi":"10.1007/s10928-024-09901-2","DOIUrl":"https://doi.org/10.1007/s10928-024-09901-2","url":null,"abstract":"Brepocitinib is an oral selective dual TYK2/JAK1 inhibitor and based on its cytokine inhibition profile is expected to provide therapeutic benefit in the treatment of plaque psoriasis. Efficacy data from a completed Phase 2a study in patients with moderate-to-severe plaque psoriasis were utilized to develop a population exposure-response model that can be employed to inform dose selection decisions for further clinical development. A modeling approach that employs the zero-inflated beta distribution was used to account for the bounded nature and distributional characteristics of the Psoriasis Area and Severity Index (PASI) score data. The developed exposure-response model provided an adequate description of the observed PASI scores across all the treatment arms tested and across both the induction and maintenance dosing periods of the study. In addition, the developed model exhibited a good predictive capacity with regard to the derived responder metrics (e.g., 75%/90%/100% improvement in PASI score [PASI75/90/100]). Clinical trial simulations indicated that the induction/maintenance dosing paradigm explored in this study does not offer any advantages from an efficacy perspective and that doses of 10, 30, and 60 mg once-daily may be suitable candidates for clinical evaluation in subsequent Phase 2b studies.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"80 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140016833","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

A population pharmacokinetics model of balovaptan to support dose selection in adult and pediatric populations 支持成人和儿童剂量选择的巴络伐坦群体药代动力学模型

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-02-03 DOI: 10.1007/s10928-023-09898-0

{"title":"A population pharmacokinetics model of balovaptan to support dose selection in adult and pediatric populations","authors":"","doi":"10.1007/s10928-023-09898-0","DOIUrl":"https://doi.org/10.1007/s10928-023-09898-0","url":null,"abstract":"<h3>Abstract</h3> Balovaptan is a brain-penetrating vasopressin receptor 1a antagonist previously investigated for the core symptoms of autism spectrum disorder (ASD). A population pharmacokinetic (PK) model of balovaptan was developed, initially to assist clinical dosing for adult and pediatric ASD studies and subsequently for new clinical indications including malignant cerebral edema (MCE) and post-traumatic stress disorder. The final model incorporates one-compartment disposition and describes time- and dose-dependent non-linear PK through empirical drug binding and a gut extraction component with turnover. An age effect on clearance observed in children was modeled by an asymptotic function that predicts adult-equivalent exposures at 40% of the adult dose for children aged 2–4 years, 70% for 5–9 years, and at the full adult dose for ≥ 10 years. The model was adapted for intravenous (IV) balovaptan dosing and combined with in vitro and ex vivo pharmacodynamic data to simulate brain receptor occupancy as a guide for dosing in a phase II trial of MCE prophylaxis after acute ischemic stroke. A sequence of three stepped-dose daily infusions of 50, 25 and 15 mg over 30 or 60 min was predicted to achieve a target occupancy of ≥ 80% in ≥ 95% of patients over a 3-day period. This model predicts both oral and IV balovaptan exposure across a wide age range and will be a valuable tool to analyze and predict its PK in new indications and target populations, including pediatric patients.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"10 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139678853","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

Population pharmacokinetic/pharmacodynamic modeling of nifekalant injection with varies dosing plan in Chinese volunteers: a randomized, blind, placebo-controlled study. 在中国志愿者中采用不同给药方案的硝苯地平注射液的群体药代动力学/药效学模型：一项随机、盲法、安慰剂对照研究。

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-02-01 Epub Date: 2023-08-11 DOI: 10.1007/s10928-023-09882-8

Juanjuan Jiang, Li Xu, Lin Chai, Li Zhang, Hong Liu, Yan Yan, Xiaoyuan Guan, Hui Sun, Lei Tian

{"title":"Population pharmacokinetic/pharmacodynamic modeling of nifekalant injection with varies dosing plan in Chinese volunteers: a randomized, blind, placebo-controlled study.","authors":"Juanjuan Jiang, Li Xu, Lin Chai, Li Zhang, Hong Liu, Yan Yan, Xiaoyuan Guan, Hui Sun, Lei Tian","doi":"10.1007/s10928-023-09882-8","DOIUrl":"10.1007/s10928-023-09882-8","url":null,"abstract":"Nifekalant hydrochloride is a class III antiarrhythmic agent which could increase the duration of the action potential and the effective refractory period of ventricular and atrial myocytes by blocking the K+ current. Nifekalant is used to prevent ventricular tachycardia/ventricular fibrillation. QT interval prolongation is the main measurable drug effect. However, due to the complicated dosing plan in clinic, the relationship among dosage, time, drug concentration and efficacy is not fully understood. In this study, a single-center, randomized, blind, dose-ascending, placebo-controlled study was conducted to explore the intrinsic characteristics of nifekalant injection in healthy Chinese volunteers by a population pharmacokinetic (PK)-pharmacodynamic (PD) model approach. 42 subjects were enrolled in this study and received one of three dose plans (loading dose on Day 1 (0.15, 0.3 or 0.5 mg/kg), loading dose followed by maintenance dose (0.2, 0.4 or 0.8 mg/kg/h) on Day 4) or vehicle. Blood samples were drawn for PK evaluation, and ECGs were recorded for QTc calculation at the designed timepoints. No Torsades de Pointes occurred during the study. The popPK model of nifekalant injection could be described by a two-compartment model with first-order elimination. The population mean clearance (CL) was 53.8 L/h. The population mean distribution volume of the central (Vc) and peripheral (Vp) compartments was 8.27 L and 45.6 L, respectively. A nonlinear dose-response (Emax) model well described the pharmacodynamic effect (QTc interval prolongation) of nifekalant. The Emax and EC50 from current study were 101 ms and 342 ng/mL, respectively.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":" ","pages":"77-87"},"PeriodicalIF":2.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10328050","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

Optimal sample selection applied to information rich, dense data. 适用于信息丰富、密集数据的最佳样本选择。

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-02-01 Epub Date: 2023-08-10 DOI: 10.1007/s10928-023-09883-7

David Wang, Tak Hung, Noelyn Hung, Paul Glue, Chris Jackson, Stephen Duffull

引用次数: 0