Journal of Pharmacokinetics and Pharmacodynamics最新文献_第9页

Target-mediated drug disposition model for drugs with N > 2 binding sites that bind to a target with one binding site N > 2 个结合位点的药物与一个结合位点的靶点结合的靶点介导药物处置模型

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-04-19 DOI: 10.1007/s10928-024-09917-8

Leonid Gibiansky, Chee M. Ng, Ekaterina Gibiansky

{"title":"Target-mediated drug disposition model for drugs with N > 2 binding sites that bind to a target with one binding site","authors":"Leonid Gibiansky, Chee M. Ng, Ekaterina Gibiansky","doi":"10.1007/s10928-024-09917-8","DOIUrl":"https://doi.org/10.1007/s10928-024-09917-8","url":null,"abstract":"The paper extended the TMDD model to drugs with more than two (N > 2) identical binding sites (N-to-one TMDD). The quasi-steady-state (N-to-one QSS), quasi-equilibrium (N-to-one QE), irreversible binding (N-to-one IB), and Michaelis–Menten (N-to-one MM) approximations of the model were derived. To illustrate properties of new equations and approximations, N = 4 case was investigated numerically. Using simulations, the N-to-one QSS approximation was compared with the full N-to-one TMDD model. As expected, and similarly to the standard TMDD for monoclonal antibodies (mAb), N-to-one QSS predictions were nearly identical to N-to-one TMDD predictions, except for times of fast changes following initiation of dosing, when equilibrium has not yet been reached. Predictions for mAbs with soluble targets (slow elimination of the complex) were simulated from the full 4-to-one TMDD model and were fitted to the 4-to-one TMDD model and to its QSS approximation. It was demonstrated that the 4-to-one QSS model provided nearly identical description of not only the observed (simulated) total drug and total target concentrations, but also unobserved concentrations of the free drug, free target, and drug-target complexes. For mAb with a membrane-bound target, the 4-to-one MM approximation adequately described the data. The 4-to-one QSS approximation converged 8 times faster than the full 4-to-one TMDD.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"103 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140625534","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 systematic evaluation of population pharmacokinetic models for polymyxin B in patients with liver and/or kidney dysfunction 对肝脏和/或肾脏功能障碍患者体内多粘菌素 B 的群体药代动力学模型进行系统评估

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-04-16 DOI: 10.1007/s10928-024-09916-9

Xueyong Li, Yu Cheng, Bingqing Zhang, Bo Chen, Yiying Chen, Yingbing Huang, Hailing Lin, Lili Zhou, Hui Zhang, Maobai Liu, Wancai Que, Hongqiang Qiu

{"title":"A systematic evaluation of population pharmacokinetic models for polymyxin B in patients with liver and/or kidney dysfunction","authors":"Xueyong Li, Yu Cheng, Bingqing Zhang, Bo Chen, Yiying Chen, Yingbing Huang, Hailing Lin, Lili Zhou, Hui Zhang, Maobai Liu, Wancai Que, Hongqiang Qiu","doi":"10.1007/s10928-024-09916-9","DOIUrl":"https://doi.org/10.1007/s10928-024-09916-9","url":null,"abstract":"Polymyxin B (PMB) is considered a last-line treatment for multidrug-resistant (MDR) gram-negative bacterial infections. Model-informed precision dosing with population pharmacokinetics (PopPK) models could help to individualize PMB dosing regimens and improve therapy. However, the external prediction ability of the established PopPK models has not been fully elaborated. This study aimed to systemically evaluate eleven PMB PopPK models from ten published literature based on a new independent population, which was divided into four different populations, patients with liver dysfunction, kidney dysfunction, liver and kidney dysfunction, and normal liver and kidney function. The whole data set consisted of 146 patients with 391 PMB concentrations. The prediction- and simulation-based diagnostics and Bayesian forecasting were conducted to evaluate model predictability. In the overall evaluation process, none of the models exhibited satisfactory predictive ability in both prediction- and simulation-based diagnostic simultaneously. However, the evaluation of the models in the subgroup of patients with normal liver and kidney function revealed improved predictive performance compared to those with liver and/or kidney dysfunction. Bayesian forecasting demonstrated enhanced predictability with the incorporation of two to three prior observations. The external evaluation highlighted a lack of consistency between the prediction results of published models and the external validation dataset. Nonetheless, Bayesian forecasting holds promise in improving the predictive performance of the models, and feedback from therapeutic drug monitoring is crucial in optimizing individual dosing regimens.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"112 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568039","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

Five multivariate Duchenne muscular dystrophy progression models bridging six-minute walk distance and MRI relaxometry of leg muscles 连接六分钟步行距离和腿部肌肉核磁共振松弛测量的五个多变量杜兴氏肌肉萎缩症进展模型

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-04-12 DOI: 10.1007/s10928-024-09910-1

Deok Yong Yoon, Michael J. Daniels, Rebecca J. Willcocks, William T. Triplett, Juan Francisco Morales, Glenn A. Walter, William D. Rooney, Krista Vandenborne, Sarah Kim

{"title":"Five multivariate Duchenne muscular dystrophy progression models bridging six-minute walk distance and MRI relaxometry of leg muscles","authors":"Deok Yong Yoon, Michael J. Daniels, Rebecca J. Willcocks, William T. Triplett, Juan Francisco Morales, Glenn A. Walter, William D. Rooney, Krista Vandenborne, Sarah Kim","doi":"10.1007/s10928-024-09910-1","DOIUrl":"https://doi.org/10.1007/s10928-024-09910-1","url":null,"abstract":"The study aimed to provide quantitative information on the utilization of MRI transverse relaxation time constant (MRI-T2) of leg muscles in DMD clinical trials by developing multivariate disease progression models of Duchenne muscular dystrophy (DMD) using 6-min walk distance (6MWD) and MRI-T2. Clinical data were collected from the prospective and longitudinal ImagingNMD study. Disease progression models were developed by a nonlinear mixed-effect modeling approach. Univariate models of 6MWD and MRI-T2 of five muscles were developed separately. Age at assessment was the time metric. Multivariate models were developed by estimating the correlation of 6MWD and MRI-T2 model variables. Full model estimation approach for covariate analysis and five-fold cross validation were conducted. Simulations were performed to compare the models and predict the covariate effects on the trajectories of 6MWD and MRI-T2. Sigmoid Imax and Emax models best captured the profiles of 6MWD and MRI-T2 over age. Steroid use, baseline 6MWD, and baseline MRI-T2 were significant covariates. The median age at which 6MWD is half of its maximum decrease in the five models was similar, while the median age at which MRI-T2 is half of its maximum increase varied depending on the type of muscle. The models connecting 6MWD and MRI-T2 successfully quantified how individual characteristics alter disease trajectories. The models demonstrate a plausible correlation between 6MWD and MRI-T2, supporting the use of MRI-T2. The developed models will guide drug developers in using the MRI-T2 to most efficient use in DMD clinical trials.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"103 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568241","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

Impact of covariate model building methods on their clinical relevance evaluation in population pharmacokinetic analyses: comparison of the full model, stepwise covariate model (SCM) and SCM+ approaches 建立协变量模型的方法对群体药代动力学分析中临床相关性评估的影响：完整模型、逐步协变量模型（SCM）和 SCM+ 方法的比较

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-04-09 DOI: 10.1007/s10928-024-09911-0

Morgane Philipp, Simon Buatois, Sylvie Retout, France Mentré

{"title":"Impact of covariate model building methods on their clinical relevance evaluation in population pharmacokinetic analyses: comparison of the full model, stepwise covariate model (SCM) and SCM+ approaches","authors":"Morgane Philipp, Simon Buatois, Sylvie Retout, France Mentré","doi":"10.1007/s10928-024-09911-0","DOIUrl":"https://doi.org/10.1007/s10928-024-09911-0","url":null,"abstract":"Covariate analysis in population pharmacokinetics is key for adjusting doses for patients. The main objective of this work was to compare the adequacy of various modeling approaches on covariate clinical relevance decision-making. The full model, stepwise covariate model (SCM) and SCM+ PsN algorithms were compared in a clinical trial simulation of a 383-patient population pharmacokinetic study mixing rich and sparse designs. A one-compartment model with first-order absorption was used. A base model including a body weight effect on CL/F and V/F and a covariate model including 4 additional covariates-parameters relationships were simulated. As for forest plots, ratios between covariates at a specific value and that of a typical individual were calculated with their 90% confidence interval (CI90) using standard errors. Covariates on CL, V and KA were considered relevant if their CI90 fell completely outside the reference area [0.8–1.2]. All approaches provided unbiased covariate ratio estimates. For covariates with a simulated effect, the 3 approaches correctly identify their clinical relevance. However, significant covariates were missed in up to 15% of cases with SCM/SCM+. For covariate with no simulated effects, the full model mainly identified them as non-relevant or with insufficient information while SCM/SCM+ mainly did not select them. SCM/SCM+ assume that non-selected covariates are non-relevant when it could be due to insufficient information, whereas the full model does not make this assumption and is faster. This study must be extended to other methods and completed by a more complex high-dimensional simulation framework.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"55 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568613","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

Model-based comparison of subcutaneous versus sublingual apomorphine administration in the treatment of motor fluctuations in Parkinson’s disease 基于模型比较皮下注射和舌下注射阿朴吗啡治疗帕金森病运动波动的效果

IF 2.5 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-04-05 DOI: 10.1007/s10928-024-09914-x

Azmi Nasser, Roberto Gomeni, Gianpiera Ceresoli-Borroni, Lanyi Xie, Gregory D. Busse, Zare Melyan, Jonathan Rubin

{"title":"Model-based comparison of subcutaneous versus sublingual apomorphine administration in the treatment of motor fluctuations in Parkinson’s disease","authors":"Azmi Nasser, Roberto Gomeni, Gianpiera Ceresoli-Borroni, Lanyi Xie, Gregory D. Busse, Zare Melyan, Jonathan Rubin","doi":"10.1007/s10928-024-09914-x","DOIUrl":"https://doi.org/10.1007/s10928-024-09914-x","url":null,"abstract":"The objective of this study was to compare the effectiveness of subcutaneous (SC) and sublingual (SL) formulations of apomorphine for the treatment of motor fluctuations in Parkinson’s disease using a pharmacokinetics (PK)/pharmacodynamics (PD) modeling approach. The PK of SC and SL apomorphine are best described by a one-compartment model with first-order absorption and a two-compartment model with delayed absorption, respectively. The PK/PD model relating apomorphine plasma concentrations to the Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores was described by a sigmoidal Emax model assuming effective concentration = drug concentration in an effect compartment. Apomorphine concentrations and UPDRS motor scores were simulated from the PK/PD models using 500 hypothetical subjects. UPDRS motor score change from baseline was evaluated using time to clinically relevant response, response duration, area under the curve, maximal response, and time to maximal response. Higher doses of each apomorphine formulation were associated with shorter time to response, longer response duration, and greater maximal response. Although the mean maximal responses to SC and SL apomorphine were comparable, the time to response was four times shorter (7 vs. 31 min) and time to maximal response was two times shorter (27 vs. 61 min) for 4 mg SC vs. 50 mg SL. Thus, faster onset of action was observed for the SC formulation compared to SL. These data may be useful for physicians when selecting “on demand” therapy for patients with Parkinson’s disease experiencing motor fluctuations.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":"12 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568150","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

Learning pharmacometric covariate model structures with symbolic regression networks. 用符号回归网络学习药效学协变量模型结构。

IF 2.2 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-04-01 Epub Date: 2023-10-21 DOI: 10.1007/s10928-023-09887-3

Ylva Wahlquist, Jesper Sundell, Kristian Soltesz

{"title":"Learning pharmacometric covariate model structures with symbolic regression networks.","authors":"Ylva Wahlquist, Jesper Sundell, Kristian Soltesz","doi":"10.1007/s10928-023-09887-3","DOIUrl":"10.1007/s10928-023-09887-3","url":null,"abstract":"Efficiently finding covariate model structures that minimize the need for random effects to describe pharmacological data is challenging. The standard approach focuses on identification of relevant covariates, and present methodology lacks tools for automatic identification of covariate model structures. Although neural networks could potentially be used to approximate covariate-parameter relationships, such approximations are not human-readable and come at the risk of poor generalizability due to high model complexity.In the present study, a novel methodology for the simultaneous selection of covariate model structure and optimization of its parameters is proposed. It is based on symbolic regression, posed as an optimization problem with a smooth loss function. This enables training of the model through back-propagation using efficient gradient computations.Feasibility and effectiveness are demonstrated by application to a clinical pharmacokinetic data set for propofol, containing infusion and blood sample time series from 1031 individuals. The resulting model is compared to a published state-of-the-art model for the same data set. Our methodology finds a covariate model structure and corresponding parameter values with a slightly better fit, while relying on notably fewer covariates than the state-of-the-art model. Unlike contemporary practice, finding the covariate model structure is achieved without an iterative procedure involving manual interactions.","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":" ","pages":"155-167"},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49678760","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

Fourteenth American Conference on Pharmacometrics (ACoP14) - Innovation and Diversity: Redefining Pharmacometrics. 第十四届美国药物计量学会议（ACoP14）--创新与多样性：重新定义药物计量学。

IF 2.2 4区医学

Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-04-01 Epub Date: 2024-02-28 DOI: 10.1007/s10928-024-09908-9

Sihem Ait-Oudhia

引用次数: 0

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