21 Result(s)
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Article
Amgen v. Sanofi: Critical Impact on the Value of Innovative Science in Antibody Discovery
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Article
Targeted Delivery of Endosomal Escape Peptides to Enhance Immunotoxin Potency and Anti-cancer Efficacy
This work describes use of anti-carcinoembryonic antigen antibodies (10H6, T84.66) for targeted delivery of an endosomal escape peptide (H6CM18) and gelonin, a type I ribosome inactivating protein. The viabili...
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Article
Investigation of the Influence of Protein-Losing Enteropathy on Monoclonal Antibody Pharmacokinetics in Mice
Protein losing enteropathy (PLE), which is characterized by substantial loss of plasma proteins into the gastrointestinal (GI) tract, is a complication of a variety of GI diseases, including inflammatory bowel...
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Article
Physiologically-based pharmacokinetic modeling to predict the clinical pharmacokinetics of monoclonal antibodies
Accurate prediction of the clinical pharmacokinetics of new therapeutic entities facilitates decision making during drug discovery, and increases the probability of success for early clinical trials. Standard ...
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Article
Sorafenib Decreases Tumor Exposure to an Anti-carcinoembryonic Antigen Monoclonal Antibody in a Mouse Model of Colorectal Cancer
In this investigation, we test the hypothesis that treatment with sorafenib, an anti-angiogenic agent, decreases tumor vascularization and, consequently, hinders the delivery of monoclonal antibodies (mAb) to ...
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Article
Scale-up of a physiologically-based pharmacokinetic model to predict the disposition of monoclonal antibodies in monkeys
Preclinical assessment of monoclonal antibody (mAb) disposition during drug development often includes investigations in non-human primate models. In many cases, mAb exhibit non-linear disposition that relates...
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Article
Pharmacodynamic modeling of chemotherapeutic effects: Application of a transit compartment model to characterize methotrexate effects in vitro
The time course of chemotherapeutic effect is often delayed relative to the time course of chemotherapeutic exposure. In many cases, this delay is difficult to characterize mathematically through the use of st...
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Article
Investigation of the Influence of Nephropathy on Monoclonal Antibody Disposition: A Pharmacokinetic Study in a Mouse Model of Diabetic Nephropathy
This study employed a mouse model to evaluate the effects of diabetic nephropathy on the pharmacokinetics of 8C2, a murine monoclonal antibody (mAb).
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Article
Predicting the effects of 8C2, a monoclonal anti-topotecan antibody, on plasma and tissue disposition of topotecan
We are investigating an inverse targeting strategy to reduce the dose limiting systemic toxicities resultant from intraperitoneal administration of topotecan, a model chemotherapeutic drug. This approach utili...
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Article
Second-generation minimal physiologically-based pharmacokinetic model for monoclonal antibodies
Minimal physiologically-based pharmacokinetic (mPBPK) models provide a sensible modeling approach when fitting only plasma (or blood) data yielding physiologically-relevant PK parameters that may provide more ...
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Article
Application of PBPK modeling to predict monoclonal antibody disposition in plasma and tissues in mouse models of human colorectal cancer
This investigation evaluated the utility of a physiologically based pharmacokinetic (PBPK) model, which incorporates model parameters representing key determinants of monoclonal antibody (mAb) target-mediated ...
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Article
Evaluation of a Catenary PBPK Model for Predicting the In Vivo Disposition of mAbs Engineered for High-Affinity Binding to FcRn
Efforts have been made to extend the biological half-life of monoclonal antibody drugs (mAbs) by increasing the affinity of mAb–neonatal Fc receptor (FcRn) binding; however, mixed results have been reported. O...
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Article
Pharmacokinetic mAb–mAb Interaction: Anti-VEGF mAb Decreases the Distribution of Anti-CEA mAb into Colorectal Tumor Xenografts
To date, there has been little investigation of the risk for drug–drug interactions involving monoclonal antibodies. The present work examined the effects of an anti-vascular endothelial growth factor (anti-VE...
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Chapter
Immune Complex Therapies for Treatment of Immune Thrombocytopenia
Approximately 30% of patients with chronic immune thrombocytopenia (ITP), a common autoimmune disease, are refractory to standard therapies. In the last several years, several published reports have suggested ...
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Article
Physiologically based pharmacokinetic model for topotecan in mice
Topotecan is a chemotherapeutic agent of choice for the second-line treatment of recurrent ovarian cancer. In this article, we have developed a physiologically based pharmacokinetic model to characterize and p...
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Article
Investigation of the Influence of FcRn on the Distribution of IgG to the Brain
It has been suggested that the neonatal Fc receptor (FcRn) is a primary determinant of the distribution of IgG to the brain. In the present report, 125I-labeled 7E3, a monoclonal IgG1 antibody, was injected intra...
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Article
Mathematical modeling of topotecan pharmacokinetics and toxicodynamics in mice
The objective of this study was to investigate the pharmacokinetics and toxicodynamics of topotecan (TPT) in mice and to develop an integrated pharmacokinetic/toxicodynamic (PK/TD) model to characterize the re...
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Article
Physiologically-based pharmacokinetic (PBPK) model to predict IgG tissue kinetics in wild-type and FcRn-knockout mice
Although it is known that FcRn, the neonatal Fc-receptor, functions to protect immune gamma globulin (IgG) from elimination, the influence of FcRn on the tissue distribution of IgG has not been quantified. In ...
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Article
Pharmacokinetic and pharmacodynamic effects of high-dose monoclonal antibody therapy in a rat model of immune thrombocytopenia
Intravenous administration of pooled, polyvalent human immunoglobulin (IVIG) has been used for over 20 years as a therapy for immune thrombocytopenia (ITP). IVIG is available in limited quantities, and clinica...
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Article
Pharmacodynamics of in Vivo Nitroglycerin Tolerance in Normal Conscious Rats: Effects of Dose and Dosing Protocol
Purpose. We examined the effects of dose and dosing protocol on the pharmacodynamics of in vivo nitroglycerin (NTG) tolerance in conscious rats. Mechanism-based pharmcokinetic/pharmacodynamic (PK/PD) models were...
