ArticlePharmaceutical research2012
Anti-neuropilin-1 (MNRP1685A): unexpected pharmacokinetic differences across species, from preclinical models to humans.
Article in Pharmaceutical research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 38 citations in OpenAlex.
- Cross-Species Extrapolation of Neonatal Fc Receptor (FcRn) Binding Affinity to Predict Monoclonal Antibody Pharmacokinetics in Humans Using Physiologically Based Pharmacokinetic Modeling (PBPK): Are We There Yet?ACS pharmacology & translational science · 2025Article
- Neuropilin Antagonists (NRPas) Block the Phosphorylation of the Cancer Therapeutic Key Factor p38α Kinase Triggering Cell Death.Molecules (Basel, Switzerland) · 2025Article
- Endothelial Neuropilin-1: a multifaced signal transducer with an emerging role in inflammation and atherosclerosis beyond angiogenesis.Biochemical Society transactions · 2024Review
- A Single Animal Species-Based Prediction of Human Clearance and First-in-Human Dose of Monoclonal Antibodies: Beyond Monkey.Antibodies (Basel, Switzerland) · 2021Article
- Pharmacokinetic prediction of an antibody in mice based on an in vitro cell-based approach using target receptor-expressing cells.Scientific reports · 2020Article
- NRP1 function and targeting in neurovascular development and eye disease.Progress in retinal and eye research · 2016Review
- Challenges and advances in the assessment of the disposition of antibody-drug conjugates.Biopharmaceutics & drug disposition · 2016Review
- A phase I study of the human monoclonal anti-NRP1 antibody MNRP1685A in patients with advanced solid tumors.Investigational new drugs · 2014Article
- VEGF targets the tumour cell.Nature reviews. Cancer · 2013Review
- Population pharmacokinetic and pharmacodynamic modeling of MNRP1685A in cynomolgus monkeys using two-target quasi-steady-state (QSS) model.Journal of pharmacokinetics and pharmacodynamics · 2012Article
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Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo compare the pharmacokinetics (PK) of MNRP1685A, a human monoclonal antibody (mAb) against neuropilin-1 (NRP1), in mice, rats, monkeys, and cancer patients from a Phase I study to model with parallel linear and nonlinear clearances.
methodsBinding characteristics of MNRP1685A in different species were evaluated using surface plasmon resonance technology. PK profiles of MNRP1685A after single and/or multiple doses in different species were analyzed using population analysis. PK parameters were compared across species.
resultsMNRP1685A binds to NRP1 in all four species tested. Consistent with the wide expression of NRP1, MNRP1685A demonstrated pronounced non-linear PK over a wide dose range. PK profiles are best described by a two-compartment model with parallel linear and nonlinear clearances. Model-derived PK parameters suggest similar in-vivo target expression levels and binding affinity to target across all species tested. However, compared to typical human/humanized mAbs, non-specific clearance of MNRP1685A was faster in mice, rats, and humans (60.3, 19.4, and 8.5 ml/day/kg), but not in monkeys (3.22 ml/day/kg).
conclusionsMonkey PK properly predicted the target-mediated clearance of MNRP1685A but underestimated its non-specific clearance in humans. This unique PK property warrants further investigation of underlying mechanisms.
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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.