ArticleThe AAPS journal2016
A Bottom-Up Whole-Body Physiologically Based Pharmacokinetic Model to Mechanistically Predict Tissue Distribution and the Rate of Subcutaneous Absorption of Therapeutic Proteins.
Article in The AAPS journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 104 citations in OpenAlex.
- Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20%: a Phase 2/3 study in Europe in patients with primary immunodeficiencies.Clinical and experimental immunology · 2017Trial
- From permeation enhancer to therapeutic enabler: Advances, applications, and translational perspectives in hyaluronidase-based drug delivery.Materials today. Bio · 2026Review
- Classification system proposed to guide the design, development, regulatory approval, and scaling of long acting, small- and macro-molecule parenteral products (CS-BLAP).Journal of pharmaceutical sciences · 2026Review
- Article
- Utilizing Minimal Physiologically Based Pharmacokinetic Modeling to Bridge Bevacizumab Pharmacokinetics from Adult to Pediatric Patients.The AAPS journal · 2025Article
- Utility of anLab on a chip · 2025Article
- Mechanistic Insights into Cytokine Antagonist-Drug Interactions: A Physiologically Based Pharmacokinetic Modelling Approach with Tocilizumab as a Case Study.Pharmaceutics · 2025Article
- Cross-species translational modelling of targeted therapeutic oligonucleotides using physiologically based pharmacokinetics.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- QSP modeling of loncastuximab tesirine with T-cell-dependent bispecific antibodies guides dose-regimen strategy.NPJ systems biology and applications · 2025Article
- Physiologically Based Pharmacokinetic Modeling of Biologic Case Studies in Monkeys and Humans Reveals the Necessity of an Additional Clearance Term.Pharmaceutics · 2025Article
- Physiology-based pharmacokinetic model with relative transcriptomics to evaluate tissue distribution and receptor occupancy of anifrolumab.CPT: pharmacometrics & systems pharmacology · 2025Article
- Comparison of monoclonal antibody disposition predictions using different physiologically based pharmacokinetic modelling platforms.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Physiologically Based Pharmacokinetic Modelling in Critically Ill Children Receiving Anakinra While on Extracorporeal Life Support.Clinical pharmacokinetics · 2024Article
- A Physiologically Based Pharmacokinetic Model Relates the Subcutaneous Bioavailability of Monoclonal Antibodies to the Saturation of FcRn-Mediated Recycling in Injection-Site-Draining Lymph Nodes.Antibodies (Basel, Switzerland) · 2024Article
- HSPiP, Computational, and Thermodynamic Model-Based Optimized Solvents for Subcutaneous Delivery of Tolterodine Tartrate and GastroPlus‑Based In Vivo Prediction in Humans: Part II.AAPS PharmSciTech · 2024Article
- Development of a physiologically-based pharmacokinetic model to simulate the pharmacokinetics of intramuscular antiretroviral drugs.CPT: pharmacometrics & systems pharmacology · 2024Article
- SubQ-Sim: A Subcutaneous Physiologically Based Biopharmaceutics Model. Part 1: The Injection and System Parameters.Pharmaceutical research · 2023Article
- Monoclonal Antibody Pharmacokinetics in Cynomolgus Monkeys Following Subcutaneous Administration: Physiologically Based Model Predictions from Physiochemical Properties.The AAPS journal · 2022Article
- Low-dose IL-2 reduces IL-21Nature communications · 2022Article
- A Non-radiometric Approach to Determine Tissue Vascular Blood Volume in Biodistribution Studies.The AAPS journal · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability to predict subcutaneous (SC) absorption rate and tissue distribution of therapeutic proteins (TPs) using a bottom-up approach is highly desirable early in the drug development process prior to clinical data being available. A whole-body physiologically based pharmacokinetic (PBPK) model, requiring only a few drug parameters, to predict plasma and interstitial fluid concentrations of TPs in humans after intravenous and subcutaneous dosing has been developed. Movement of TPs between vascular and interstitial spaces was described by considering both convection and diffusion processes using a 2-pore framework. The model was optimised using a variety of literature sources, such as tissue lymph/plasma concentration ratios in humans and animals, information on the percentage of dose absorbed following SC dosing via lymph in animals and data showing loss of radiolabelled IgG from the SC dosing site in humans. The resultant model was used to predict t max and plasma concentration profiles for 12 TPs (molecular weight 8-150 kDa) following SC dosing. The predicted plasma concentration profiles were generally comparable to observed data. t max was predicted within 3-fold of reported values, with one third of the predictions within 0.8-1.25-fold. There was no systematic bias in simulated C max values, although a general trend for underprediction of t max was observed. No clear trend between prediction accuracy of t max and TP isoelectric point or molecular size was apparent. The mechanistic whole-body PBPK model described here can be applied to predict absorption rate of TPs into blood and movement into target tissues following SC dosing.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.