ArticlePharmaceutical research2012
Investigation of the mechanism of clearance of AMG 386, a selective angiopoietin-1/2 neutralizing peptibody, in splenectomized, nephrectomized, and FcRn knockout rodent models.
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 5 papers.
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Who cites it
5 citing papers in PubMed, 15 citations in OpenAlex.
- Blinatumomab, a Bispecific T-cell Engager (BiTE(®)) for CD-19 Targeted Cancer Immunotherapy: Clinical Pharmacology and Its Implications.Clinical pharmacokinetics · 2016Trial
- 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
- Pediatric Phase I Trial and Pharmacokinetic Study of Trebananib in Relapsed Solid Tumors, Including Primary Tumors of the Central Nervous System ADVL1115: A Children's Oncology Group Phase I Consortium Report.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Review
- Pharmacokinetic drug-drug interaction study of the angiopoietin-1/angiopoietin-2-inhibiting peptibody trebananib (AMG 386) and paclitaxel in patients with advanced solid tumors.Investigational new drugs · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo investigate the mechanisms of clearance of AMG 386, an investigational recombinant peptide-Fc fusion protein (peptibody) that blocks tumor angiogenesis by neutralizing the interaction between angiopoietin-1 and -2 and the Tie2 receptor.
methodsThe role of the neonatal Fc receptor (FcRn) in AMG 386 clearance was assessed in wild-type and FcRn-knockout mice; the roles of the spleen and kidneys were assessed in splenectomized and 5/6th nephrectomized rats, respectively, compared with sham-operated rats. Animals were administered AMG 386 as a single intravenous dose of 3 or 10 mg/kg. Blood samples for pharmacokinetic analysis were collected periodically throughout a 504-hour postdose period.
resultsCompared with wild-type mice, AMG 386 clearance in FcRn-knockout mice was 18-fold faster at the 3-mg/kg dose (FcRn knockout, 13.2 mL/h/kg; wild-type, 0.728 mL/h/kg) and 14-fold faster at the 10-mg/kg dose (FcRn knockout, 10.7 mL/h/kg; wild-type, 0.777 mL/h/kg). Clearance in nephrectomized rats was slower than in sham-operated rats at both the 3-mg/kg dose (nephrectomized, 1.23 mL/h/kg; sham-operated, 1.75 mL/h/kg) and the 10-mg/kg dose (nephrectomized, 1.14 mL/h/kg; sham-operated, 1.65 mL/h/kg). Splenectomy had no apparent effect on the pharmacokinetics of AMG 386.
conclusionsThe FcRn is integral to maintaining circulating levels of AMG 386 in mice. Renal clearance contributed approximately 30% to total AMG 386 clearance in rats.
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