ArticlePharmaceutical research2014
Investigation of the influence of nephropathy on monoclonal antibody disposition: a pharmacokinetic study in a mouse model of diabetic nephropathy.
Article in Pharmaceutical research, 2014. 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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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.
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Who cites it
5 citing papers in PubMed, 11 citations in OpenAlex.
- Rodent models to study type 1 and type 2 diabetes induced human diabetic nephropathy.Molecular biology reports · 2023Review
- Immunoglobulin G Is a Novel Substrate for the Endocytic Protein Megalin.The AAPS journal · 2021Article
- Understanding Inter-Individual Variability in Monoclonal Antibody Disposition.Antibodies (Basel, Switzerland) · 2019Review
- Investigation of the Influence of Protein-Losing Enteropathy on Monoclonal Antibody Pharmacokinetics in Mice.The AAPS journal · 2017Article
- Effect of Type 2 Diabetes Mellitus and Diabetic Nephropathy on IgG Pharmacokinetics and Subcutaneous Bioavailability in the Rat.The AAPS journal · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThis study employed a mouse model to evaluate the effects of diabetic nephropathy on the pharmacokinetics of 8C2, a murine monoclonal antibody (mAb).
methodsStreptozotocin (STZ) was administered to mice to induce diabetic nephropathy (125 mg/kg/day × 2). Mice were grouped (n = 8-10) based on time after STZ-treatment (control, 1, 2, 3, 4, or 6 weeks), and injected intravenously with 10 mg/kg 8C2. Blood samples were collected up to 7 days, and 8C2 plasma concentrations were determined via immunoassay. Inulin clearance and urinary albumin excretion rate (UAE) were determined to assess renal function.
resultsUAE, inulin clearance, and 8C2 clearance increased significantly following STZ. Comparing control and 6 week STZ-treatment groups, UAE and inulin clearance increased from 25.7 ± 3.3 to 99.3 ± 13.7 μg/day, and from 421 ± 31 to 584 ± 78 μl/min. 8C2 clearance increased from 121 ± 12.5 to 228 ± 61 μl/hr/kg (p < 0.01). 8C2 clearance was highly correlated with UAE (r(2): 0.731). Inclusion of UAE as a covariate in population modeling explained significant residual variability in 8C2 clearance.
conclusionsThe clearance of 8C2 increased significantly in STZ-treated mice. Population pharmacokinetic modeling suggests that UAE has potential for use in predicting mAb clearance in subjects with diabetic nephropathy, possibly assisting in the individualization of mAb dosing.
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