ArticlePharmaceutical research2011
Complex pharmacokinetics of a humanized antibody against human amyloid beta peptide, anti-abeta Ab2, in nonclinical species.
Article in Pharmaceutical research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 50 citations in OpenAlex.
- Physiologically Based Pharmacokinetic Modeling to Characterize the Effect of Molecular Charge on Whole-Body Disposition of Monoclonal Antibodies.The AAPS journal · 2023Article
- Pharmacologic Considerations in the Disposition of Antibodies and Antibody-Drug Conjugates in Preclinical Models and in Patients.Antibodies (Basel, Switzerland) · 2019Review
- Next generation antibody drugs: pursuit of the 'high-hanging fruit'.Nature reviews. Drug discovery · 2018Review
- Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins.Protein & cell · 2018Review
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- Engineering the surface properties of a human monoclonal antibody prevents self-association and rapid clearance in vivo.Scientific reports · 2016Article
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- Evaluating the Use of Antibody Variable Region (Fv) Charge as a Risk Assessment Tool for Predicting Typical Cynomolgus Monkey Pharmacokinetics.The Journal of biological chemistry · 2015Article
- Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics.Journal of pharmacokinetics and pharmacodynamics · 2015Review
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- Challenges and opportunities in absorption, distribution, metabolism, and excretion studies of therapeutic biologics.The AAPS journal · 2012Review
- ADME of biologics-what have we learned from small molecules?The AAPS journal · 2012Review
- Anti-neuropilin-1 (MNRP1685A): unexpected pharmacokinetic differences across species, from preclinical models to humans.Pharmaceutical research · 2012Article
- Identification of polymorphisms in genes of the immune system in cynomolgus macaques.Mammalian genome : official journal of the International Mammalian Genome Society · 2012Article
- Pharmacokinetics and toxicology of therapeutic proteins: Advances and challenges.World journal of biological chemistry · 2012Article
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- Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAnti-Aβ Ab2 (Ab2) is a humanized monoclonal antibody against amino acids 3-6 of primate (but not rodent) amyloid β (Aβ) and is being evaluated for the treatment of Alzheimer's disease (AD). This study was conducted to predict the human pharmacokinetics of Ab2.
methodsIn vivo PK profile of Ab2 in preclinical species and in vitro mechanistic studies in preclinical and human systems were used for pharmacokinetic predictions.
resultsIn Tg2576 and PSAPP mice that have ~100-fold higher circulating levels of human Aβ compared to humans, elimination of Ab2 was target-mediated, such that exposure was 5-10 fold lower compared to wild-type rodents or to PDAPP mice that have human Aβ concentrations in plasma similar to humans. In cynomolgus monkeys, the t(1/2) of Ab2 was faster (<2.5 days) compared to that of the control antibody (~13 days). The fast elimination of Ab2 in cynomolgus monkeys was linked to off-target binding to cynomolgus monkey fibrinogen that was also causing incomplete recovery of Ab2 in cynomolgus monkey serum in blood partitioning experiments. Ab2 had significantly weaker to undetectable binding to human (and mouse) fibrinogen and had good recovery in human serum in blood partitioning experiments.
conclusionsThese data predict that elimination of Ab2 in healthy or AD humans is expected to be slow, with t(1/2) similar to that observed for other humanized antibodies.
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