ArticleThe AAPS journal2015
Quantitative prediction of human pharmacokinetics for mAbs exhibiting target-mediated disposition.
Article in The AAPS journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The trial behind it
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Who cites it
29 citing papers in PubMed.
- Translational Pharmacokinetic/Pharmacodynamic Analysis of MYO-029 Antibody for Muscular Dystrophy.Clinical and translational science · 2016Trial
- NI-3201 Is a Bispecific Antibody Mediating PD-L1-Dependent CD28 Co-stimulation on T Cells for Enhanced Tumor Control.Cancer immunology research · 2025Article
- Local depletion of large molecule drugs due to target binding in tissue interstitial space.CPT: pharmacometrics & systems pharmacology · 2024Review
- Prospective approaches to gene therapy computational modeling - spotlight on viral gene therapy.Journal of pharmacokinetics and pharmacodynamics · 2024Review
- Comparative pharmacokinetics of porcine and human anti-influenza hemagglutinin monoclonal antibodies in outbred pigs and minipigs.Frontiers in immunology · 2024Article
- Article
- Translation of the efficacy of antibody-drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88.Clinical and translational science · 2023Article
- Review of the Existing Translational Pharmacokinetics Modeling Approaches Specific to Monoclonal Antibodies (mAbs) to Support the First-In-Human (FIH) Dose Selection.International journal of molecular sciences · 2022Review
- Recent Advances in Translational Pharmacokinetics and Pharmacodynamics Prediction of Therapeutic Antibodies Using Modeling and Simulation.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Comparison of Various Approaches to Translate Non-Linear Pharmacokinetics of Monoclonal Antibodies from Cynomolgus Monkey to Human.European journal of drug metabolism and pharmacokinetics · 2021Article
- A target-mediated drug disposition population pharmacokinetic model of GC1118, a novel anti-EGFR antibody, in patients with solid tumors.Clinical and translational science · 2021Article
- Evolution of the Systems Pharmacokinetics-Pharmacodynamics Model for Antibody-Drug Conjugates to Characterize Tumor Heterogeneity andThe Journal of pharmacology and experimental therapeutics · 2020Article
- Article
- A Cell-Level Systems PK-PD Model to Characterize In Vivo Efficacy of ADCs.Pharmaceutics · 2019Article
- Design and Conduct Considerations for First-in-Human Trials.Clinical and translational science · 2019Article
- A pre-clinical quantitative model predicts the pharmacokinetics/pharmacodynamics of an anti-BDCA2 monoclonal antibody in humans.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Translational PK-PD modeling analysis of MCLA-128, a HER2/HER3 bispecific monoclonal antibody, to predict clinical efficacious exposure and dose.Investigational new drugs · 2018Article
- Article
- Article
- Quantitative Systems Pharmacology Model of hUGT1A1-modRNA Encoding for the UGT1A1 Enzyme to Treat Crigler-Najjar Syndrome Type 1.CPT: pharmacometrics & systems pharmacology · 2018Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Prediction of human pharmacokinetics (PK) can be challenging for monoclonal antibodies (mAbs) exhibiting target-mediated drug disposition (TMDD). In this study, we performed a quantitative analysis of a diverse set of six mAbs exhibiting TMDD to explore translational rules that can be utilized to predict human PK. A TMDD model with rapid-binding approximation was utilized to fit PK and PD (i.e., free and/or total target levels) data, and average absolute fold error (AAFE) was calculated for each model parameter. Based on the comparative analysis, translational rules were developed and applied to a test antibody not included in the original analysis. AAFE of less than two-fold was observed between monkey and human for baseline target levels (R 0), body-weight (BW) normalized central elimination rate (K el/BW(-0.25)) and central volume (V c/BW(1.0)). AAFE of less than three-fold was estimated for the binding affinity constant (K D). The other four parameters, i.e., complex turnover rate (K int), target turnover rate (K deg), central to peripheral distribution rate constant (K pt) and peripheral to central rate constant (K tp) were poorly correlated between monkey and human. The projected human PK of test antibody based on the translation rules was in good agreement with the observed nonlinear PK. In conclusion, we recommend a TMDD model-based prediction approach that integrates in vitro human biomeasures and in vivo preclinical data using translation rules developed in this study.
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