ArticleInternational journal of pharmaceutics2014
PK/TD modeling for prediction of the effects of 8C2, an anti-topotecan mAb, on topotecan-induced toxicity in mice.
Article in International journal of pharmaceutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
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- Recent Advances in Translational Pharmacokinetics and Pharmacodynamics Prediction of Therapeutic Antibodies Using Modeling and Simulation.Pharmaceuticals (Basel, Switzerland) · 2022Review
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- Physiologically-based modeling of monoclonal antibody pharmacokinetics in drug discovery and development.Drug metabolism and pharmacokinetics · 2019Review
- "Catch-and-Release" Anti-Carcinoembryonic Antigen Monoclonal Antibody Leads to Greater Plasma and Tumor Exposure in a Mouse Model of Colorectal Cancer.The Journal of pharmacology and experimental therapeutics · 2018Article
- Investigation of the Influence of Protein-Losing Enteropathy on Monoclonal Antibody Pharmacokinetics in Mice.The AAPS journal · 2017Article
- Development of a Translational Physiologically Based Pharmacokinetic Model for Antibody-Drug Conjugates: a Case Study with T-DM1.The AAPS journal · 2017Article
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- Unraveling the pharmacokinetic interaction of ticagrelor and MEDI2452 (Ticagrelor antidote) by mathematical modeling.CPT: pharmacometrics & systems pharmacology · 2016Article
- Application of Pharmacokinetic-Pharmacodynamic Modeling and Simulation for Antibody-Drug Conjugate Development.Pharmaceutical research · 2015Review
- Toward sensitive and accurate analysis of antibody biotherapeutics by liquid chromatography coupled with mass spectrometry.Drug metabolism and disposition: the biological fate of chemicals · 2014Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
To facilitate the development of an inverse targeting strategy, where anti-topotecan antibodies are administered to prevent systemic toxicity following intraperitoneal topotecan, a pharmacokinetic/toxicodynamic (PK/TD) model was developed and evaluated. The pharmacokinetics of 8C2, a monoclonal anti-topotecan antibody, were assessed following IV and SC administration, and the data were characterized using a two compartmental model with nonlinear absorption and elimination. A hybrid PK model was constructed by combining a PBPK model for topotecan with the two-compartment model for 8C2, and the model was employed to predict the disposition of topotecan, 8C2, and the topotecan-8C2 complex. The model was linked to a toxicodynamic model for topotecan-induced weight-loss, and simulations were conducted to predict the effects of 8C2 on the toxicity of topotecan in mice. Increasing the molar dose ratio of 8C2 to topotecan resulted in a dose-dependent decrease in the unbound (i.e., not bound to 8C2) topotecan exposure in plasma (AUCf) and a decrease in the extent of topotecan-induced weight-loss. Consistent with model predictions, toxicodynamic experiments showed substantial reduction in the percent nadir weight loss observed with 30 mg/kg IP topotecan after co-administration of 8C2 (20 ± 8% vs. 10 ± 8%). The investigation supports the use of anti-topotecan mAb to reduce the systemic toxicity of IP topotecan chemotherapy.
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