SynthesismAbs
A model-based meta-analysis of monoclonal antibody pharmacokinetics to guide optimal first-in-human study design.
Synthesis in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Applications of Model-Based Meta-Analysis in Drug Development.Pharmaceutical research · 2022Pooled it
- Optimizing clinical dosing of combination broadly neutralizing antibodies for HIV prevention.PLoS computational biology · 2022Pooled it
- Population Pharmacokinetics and Pharmacodynamics of Depemokimab in People with Asthma and Chronic Rhinosinusitis with Nasal Polyps.Journal of clinical pharmacology · 2026Trial
- Bispecific 10E8.4/iMab broadly neutralizing antibody in people with or without HIV-1: a partially randomized phase 1 trial.Nature medicine · 2026Trial
- Pharmacokinetics and safety of subcutaneous nivolumab: results from the phase I/II CheckMate 8KX study.Journal for immunotherapy of cancer · 2025Trial
- Target-Mediated Drug Disposition Pharmacokinetic/Pharmacodynamic Model-Informed Dose Selection for the First-in-Human Study of AVB-S6-500.Clinical and translational science · 2020Trial
- Population pharmacokinetics, exposure-safety, and immunogenicity of atezolizumab in pediatric and young adult patients with cancer.Journal for immunotherapy of cancer · 2019Trial
- Trial
- A new pharmacokinetic model forScientific reports · 2018Trial
- Population pharmacokinetic and pharmacodynamic analysis of BIIB023, an anti-TNF-like weak inducer of apoptosis (anti-TWEAK) monoclonal antibody.British journal of clinical pharmacology · 2016Trial
- One Model to Dose Them All: A Population Pharmacokinetic Model for Multiple Aminoglycosides Across the Human Lifespan.Journal of clinical pharmacology · 2026Article
- Optimizing Clinical Study Designs for CAR-T Cell Therapy: Development of an Efficient Sampling Strategy Through Optimal Experimental Design.CPT: pharmacometrics & systems pharmacology · 2026Article
- Mechanistic modeling of FcRn-dependent IgG drug interactions: Clinical applications and dosing implications.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Clinical Pharmacology Perspective on Direct-To-Subcutaneous Dosing of T Cell Engagers in Oncology First-In-Human Studies.Clinical and translational science · 2026Review
- Clinical Pharmacology Approaches to Predict Efficacy of Monoclonal Antibodies Against Emerging SARS-CoV-2 Variants.Clinical and translational science · 2025Review
- Dose finding in early-phase human immunodeficiency virus type 1 prevention monoclonal antibody clinical trials.Clinical trials (London, England) · 2025Review
- A model-based approach using GSK3772847, an anti-interleukin-33 receptor monoclonal antibody, as a showcase to predict SC administration PK and free target dynamics based on PK and total target measurements after IV administration.CPT: pharmacometrics & systems pharmacology · 2025Article
- Impact of LS Mutation on Pharmacokinetics of Preventive HIV Broadly Neutralizing Monoclonal Antibodies: A Cross-Protocol Analysis of 16 Clinical Trials in People without HIV.Pharmaceutics · 2024Article
- Modeling the subcutaneous pharmacokinetics of antibodies co-administered with rHuPH20.Clinical and translational science · 2024Article
- Advancing Subcutaneous Dosing Regimens for Biotherapeutics: Clinical Strategies for Expedited Market Access.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The objectives of this retrospective analysis were (1) to characterize the population pharmacokinetics (popPK) of four different monoclonal antibodies (mAbs) in a combined analysis of individual data collected during first-in-human (FIH) studies and (2) to provide a scientific rationale for prospective design of FIH studies with mAbs. The data set was composed of 171 subjects contributing a total of 2716 mAb serum concentrations, following intravenous (IV) and subcutaneous (SC) doses. mAb PK was described by an open 2-compartment model with first-order elimination from the central compartment and a depot compartment with first-order absorption. Parameter values obtained from the popPK model were further used to generate optimal sampling times for a single dose study. A robust fit to the combined data from four mAbs was obtained using the 2-compartment model. Population parameter estimates for systemic clearance and central volume of distribution were 0.20 L/day and 3.6 L with intersubject variability of 31% and 34%, respectively. The random residual error was 14%. Differences (> 2-fold) in PK parameters were not apparent across mAbs. Rich designs (22 samples/subject), minimal designs for popPK (5 samples/subject), and optimal designs for non-compartmental analysis (NCA) and popPK (10 samples/subject) were examined by stochastic simulation and estimation. Single-dose PK studies for linear mAbs executed using the optimal designs are expected to yield high-quality model estimates, and accurate capture of NCA estimations. This model-based meta-analysis has determined typical popPK values for four mAbs with linear elimination and enabled prospective optimization of FIH study designs, potentially improving the efficiency of FIH studies for this class of therapeutics.
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Registered trials
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.