Journal of Pharmacokinetics and Pharmacodynamics最新文献_第8页

Correction to: Training the next generation of pharmacometric modelers: a multisector perspective. 更正：培训下一代药物计量学建模人员：多部门视角。

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-02-01 DOI: 10.1007/s10928-023-09885-5

Peter L Bonate, Jeffrey S Barrett, Sihem Ait-Oudhia, Richard Brundage, Brian Corrigan, Stephen Duffull, Marc Gastonguay, Mats O Karlsson, Shinichi Kijima, Andreas Krause, Mark Lovern, Matthew M Riggs, Michael Neely, Daniele Ouellet, Elodie L Plan, Gauri G Rao, Joseph Standing, Justin Wilkins, Hao Zhu

引用次数: 0

Characterization of anti-drug antibody dynamics using a bivariate mixed hidden-markov model by nonlinear-mixed effects approach. 通过非线性混合效应方法，使用双变量混合隐马尔可夫模型表征抗药物抗体动力学。

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-02-01 Epub Date: 2023-11-09 DOI: 10.1007/s10928-023-09890-8

Ari Brekkan, Rocío Lledo-Garcia, Brigitte Lacroix, Siv Jönsson, Mats O Karlsson, Elodie L Plan

{"title":"Characterization of anti-drug antibody dynamics using a bivariate mixed hidden-markov model by nonlinear-mixed effects approach.","authors":"Ari Brekkan, Rocío Lledo-Garcia, Brigitte Lacroix, Siv Jönsson, Mats O Karlsson, Elodie L Plan","doi":"10.1007/s10928-023-09890-8","DOIUrl":"10.1007/s10928-023-09890-8","url":null,"abstract":"Biological therapies may act as immunogenic triggers leading to the formation of anti-drug antibodies (ADAs). Population pharmacokinetic (PK) models can be used to characterize the relationship between ADA and drug disposition but often rely on the ADA bioassay results, which may not be sufficiently sensitive to inform on this characterization.In this work, a methodology that could help to further elucidate the underlying ADA production and impact on the drug disposition was explored. A mixed hidden-Markov model (MHMM) was developed to characterize the underlying (hidden) formation of ADA against the biologic, using certolizumab pegol (CZP), as a test drug. CZP is a PEGylated Fc free TNF-inhibitor used in the treatment of rheumatoid arthritis and other chronic inflammatory diseases.The bivariate MHMM used information from plasma drug concentrations and ADA measurements, from six clinical studies (n = 845), that were correlated through a bivariate Gaussian function to infer about two hidden states; production and no-production of ADA influencing PK. Estimation of inter-individual variability was not supported in this case. Parameters associated with the observed part of the model were reasonably well estimated while parameters associated with the hidden part were less precise. Individual state sequences obtained using a Viterbi algorithm suggested that the model was able to determine the start of ADA production for each individual, being a more assay-independent methodology than traditional population PK. The model serves as a basis for identification of covariates influencing the ADA formation, and thus has the potential to identify aspects that minimize its impact on PK and/or efficacy.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":" ","pages":"65-75"},"PeriodicalIF":2.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10884144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71521891","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

Training the next generation of pharmacometric modelers: a multisector perspective. 培训下一代药物计量学建模人员：多部门视角。

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-02-01 Epub Date: 2023-08-13 DOI: 10.1007/s10928-023-09878-4

Peter L Bonate, Jeffrey S Barrett, Sihem Ait-Oudhia, Richard Brundage, Brian Corrigan, Stephen Duffull, Marc Gastonguay, Mats O Karlsson, Shinichi Kijima, Andreas Krause, Mark Lovern, Matthew M Riggs, Michael Neely, Daniele Ouellet, Elodie L Plan, Gauri G Rao, Joseph Standing, Justin Wilkins, Hao Zhu

{"title":"Training the next generation of pharmacometric modelers: a multisector perspective.","authors":"Peter L Bonate, Jeffrey S Barrett, Sihem Ait-Oudhia, Richard Brundage, Brian Corrigan, Stephen Duffull, Marc Gastonguay, Mats O Karlsson, Shinichi Kijima, Andreas Krause, Mark Lovern, Matthew M Riggs, Michael Neely, Daniele Ouellet, Elodie L Plan, Gauri G Rao, Joseph Standing, Justin Wilkins, Hao Zhu","doi":"10.1007/s10928-023-09878-4","DOIUrl":"10.1007/s10928-023-09878-4","url":null,"abstract":"The current demand for pharmacometricians outmatches the supply provided by academic institutions and considerable investments are made to develop the competencies of these scientists on-the-job. Even with the observed increase in academic programs related to pharmacometrics, this need is unlikely to change in the foreseeable future, as the demand and scope of pharmacometrics applications keep expanding. Further, the field of pharmacometrics is changing. The field largely started when Lewis Sheiner and Stuart Beal published their seminal papers on population pharmacokinetics in the late 1970's and early 1980's and has continued to grow in impact and use since its inception. Physiological-based pharmacokinetics and systems pharmacology have grown rapidly in scope and impact in the last decade and machine learning is just on the horizon. While all these methodologies are categorized as pharmacometrics, no one person can be an expert in everything. So how do you train future pharmacometricians? Leading experts in academia, industry, contract research organizations, clinical medicine, and regulatory gave their opinions on how to best train future pharmacometricians. Their opinions were collected and synthesized to create some general recommendations.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":" ","pages":"5-31"},"PeriodicalIF":2.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10531805","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

Thoughts on plagiarism and the case against Claudine Gay. 关于剽窃和克劳迪娜-盖伊案件的思考。

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-02-01 DOI: 10.1007/s10928-024-09904-z

Peter L Bonate

引用次数: 0

Correction to: Classical structural identifiability methodology applied to low-dimensional dynamic systems in receptor theory. 更正：经典结构可识别性方法应用于受体理论中的低维动态系统。

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-02-01 DOI: 10.1007/s10928-023-09879-3

Carla White, Vivi Rottschäfer, Lloyd Bridge

引用次数: 0

Correction: External control arms for rare diseases: building a body of supporting evidence. 更正：罕见疾病的外部控制臂：建立支持证据库。

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-02-01 DOI: 10.1007/s10928-024-09900-3

Artak Khachatryan, Stephanie H Read, Terri Madison

引用次数: 0

Classical structural identifiability methodology applied to low-dimensional dynamic systems in receptor theory. 将经典的结构可识别性方法应用于受体理论中的低维动态系统。

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-02-01 Epub Date: 2023-06-30 DOI: 10.1007/s10928-023-09870-y

Carla White, Vivi Rottschäfer, Lloyd Bridge

{"title":"Classical structural identifiability methodology applied to low-dimensional dynamic systems in receptor theory.","authors":"Carla White, Vivi Rottschäfer, Lloyd Bridge","doi":"10.1007/s10928-023-09870-y","DOIUrl":"10.1007/s10928-023-09870-y","url":null,"abstract":"Mathematical modelling has become a key tool in pharmacological analysis, towards understanding dynamics of cell signalling and quantifying ligand-receptor interactions. Ordinary differential equation (ODE) models in receptor theory may be used to parameterise such interactions using timecourse data, but attention needs to be paid to the theoretical identifiability of the parameters of interest. Identifiability analysis is an often overlooked step in many bio-modelling works. In this paper we introduce structural identifiability analysis (SIA) to the field of receptor theory by applying three classical SIA methods (transfer function, Taylor Series and similarity transformation) to ligand-receptor binding models of biological importance (single ligand and Motulsky-Mahan competition binding at monomers, and a recently presented model of a single ligand binding at receptor dimers). New results are obtained which indicate the identifiable parameters for a single timecourse for Motulsky-Mahan binding and dimerised receptor binding. Importantly, we further consider combinations of experiments which may be performed to overcome issues of non-identifiability, to ensure the practical applicability of the work. The three SIA methods are demonstrated through a tutorial-style approach, using detailed calculations, which show the methods to be tractable for the low-dimensional ODE models.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":" ","pages":"39-63"},"PeriodicalIF":2.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10884104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10250235","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

Special issue: Model-informed drug development in rare diseases: connecting the dots in an information rich ecosystem. 特刊:基于模型的罕见疾病药物开发:在信息丰富的生态系统中连接各个点。

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2023-12-01 Epub Date: 2023-04-27 DOI: 10.1007/s10928-023-09862-y

Rajesh Krishna

引用次数: 0

Rare oncology therapeutics: review of clinical pharmacology package of drug approvals (2019-2023) by US FDA, best practices and recommendations. 罕见肿瘤治疗学：美国食品药品监督管理局对临床药理学药物批准包（2019-2023）的审查、最佳实践和建议。

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2023-12-01 Epub Date: 2023-11-04 DOI: 10.1007/s10928-023-09896-2

Amitava Mitra, Jong Bong Lee, Douglas Steinbach, Anasuya Hazra, Rajesh Krishna

{"title":"Rare oncology therapeutics: review of clinical pharmacology package of drug approvals (2019-2023) by US FDA, best practices and recommendations.","authors":"Amitava Mitra, Jong Bong Lee, Douglas Steinbach, Anasuya Hazra, Rajesh Krishna","doi":"10.1007/s10928-023-09896-2","DOIUrl":"10.1007/s10928-023-09896-2","url":null,"abstract":"There are many challenges with rare diseases drug development and rare oncology indications are not different. To understand the regulatory landscape as it relates to application of clinical pharmacology principles in rare oncology product development, we reviewed publicly available information of 39 approvals by US FDA between January 2019 and March 2023. The objective was to understand the expected clinical pharmacology studies and knowledge base in such approvals. Model informed drug development (MIDD) applications were also reviewed, as such approaches are expected to play a critical role in filling clinical pharmacology gaps in rare oncology, where number of clinical trials and size of these trials will perhaps continue to be small. The findings highlighted how clinical pharmacology contributed to the evidence of effectiveness, dose optimization and elucidation of intrinsic and extrinsic factors affecting drug's behavior. Clinical pharmacology studies were often integrated with modeling in many of the NDAs/BLAs. Of the post marketing requirements (PMR) received, 18% were for dose optimization, 49% for DDI, 8% for QTc, 49% for specific population, and 5% for food effect. Two post marketing commitments (PMC) were issued for immunogenicity of the 11 biologics submissions. 15% (6 of 39) of the submissions used maximum tolerated dose (MTD) to advance their molecule into Phase 2 studies. Of them 3 approvals received PMR for dose optimization. 3 + 3 was the most prevalent Phase 1 design with use in 74% of the New Drug Applications (NDA)/Biologic License Applications (BLA) reviewed. Rest used innovative approaches such as BLRM, BOIN or mTPi, with BLRM being the most common. Seamless clinical pharmacology and MIDD approaches are paramount for rare oncology drug development.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":" ","pages":"475-493"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482796","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 modeling and dosing simulation of avalglucosidase alfa for selecting alternative dosing regimen in pediatric patients with late-onset pompe disease. 儿童迟发性庞贝病患者avalalglucosidase alfa的人群药代动力学建模和给药模拟选择替代给药方案。

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2023-12-01 Epub Date: 2023-08-03 DOI: 10.1007/s10928-023-09874-8

Gilles Tiraboschi, David Marchionni, Gilles Tuffal, David Fabre, Jean-Marie Martinez, Kristina An Haack, Patrick Miossec, Barbara Kittner, Nadia Daba, Fabrice Hurbin

{"title":"Population pharmacokinetic modeling and dosing simulation of avalglucosidase alfa for selecting alternative dosing regimen in pediatric patients with late-onset pompe disease.","authors":"Gilles Tiraboschi, David Marchionni, Gilles Tuffal, David Fabre, Jean-Marie Martinez, Kristina An Haack, Patrick Miossec, Barbara Kittner, Nadia Daba, Fabrice Hurbin","doi":"10.1007/s10928-023-09874-8","DOIUrl":"10.1007/s10928-023-09874-8","url":null,"abstract":"Avalglucosidase alfa (AVAL) was approved in the United States (2021) for patients with late-onset Pompe disease (LOPD), aged ≥ 1 year. In the present study, pharmacokinetic (PK) simulations were conducted to propose alternative dosing regimens for pediatric LOPD patients based on a bodyweight cut-off. Population PK (PopPK) analysis was performed using nonlinear mixed effect modeling approach on pooled data from three clinical trials with LOPD patients, and a phase 2 study (NCT03019406) with infantile-onset Pompe disease (IOPD: 1-12 years) patients. A total of 2257 concentration-time points from 91 patients (LOPD, n = 75; IOPD, n = 16) were included in the analysis. The model was bodyweight dependent allometric scaling with time varying bodyweight included on clearance and distribution volume. Simulations were performed for two dosing regimens (20 mg/kg or 40 mg/kg) with different bodyweight cut-off (25, 30, 35 and 40 kg) by generating virtual pediatric (1-17 years) and adult patients. Corresponding simulated individual exposures (maximal concentration, Cmax and area under the curve in the 2-week dosing interval, AUC2W), and distributions were calculated. It was found that dosing of 40 mg/kg and 20 mg/kg in pediatric patients < 30 kg and ≥ 30 kg, respectively, achieved similar AVAL exposure (based on AUC2W) to adult patients receiving 20 mg/kg. PK simulations conducted on the basis of this model provided supporting data for the currently approved US labelling for dosing adapted bodyweight in LOPD patients ≥ 1 year by USFDA.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":" ","pages":"461-474"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9927814","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