Minimal Physiologically-based Pharmacokinetic Model to Investigate the Effect of Charge on the Pharmacokinetics of Humanized anti-HCV-E2 IgG Antibodies in Sprague-Dawley Rats.

Purpose: To develop a minimal physiologically-based pharmacokinetic (mPBPK) model in quantifying the relationships between the charge and pharmacokinetics (PK) of therapeutic monoclonal IgG antibody (TMAb).

Methods: PK data used in this study were native IgG and five humanized anti-HCVE2-IgG antibodies in rats. Different models that related the effect of charge on interstitial distribution, transcapillary transport, and cellular uptake for FcRn-mediated metabolism were tested.

Quantitative Systems Pharmacology Model of Chimeric Antigen Receptor T-Cell Therapy.

Chimeric antigen receptor T-cell (CART) therapy is a new and promising cancer therapy. However, severe toxicity due to cytokine release syndrome (CRS) in CART-treated patients highlighted the possible danger of this new therapy. Disease burden and CART doses are the potential factors associated with CRS but the detail relationships between these factors and the severity of the CRS remain largely unknown.

Minimal physiologically-based pharmacokinetic model to investigate the effect of pH dependent FcRn affinity and the endothelial endocytosis on the pharmacokinetics of anti-VEGF humanized IgG1 antibody in cynomolgus monkey.

In this study, we developed a first minimal physiologically-based pharmacokinetic (mPBPK) model to investigate the complex interaction effects of endocytosis rate/FcRn binding affinity at both acidic/physiological pH on the pharmacokinetics (PK) of the anti-VEGF IgG antibodies. The data used in this study were the PK of the native IgG and humanized anti-VEGF IgG antibodies with a wide range FcRn-binding at both acidic and physiological pH in the cynomolgus monkey. The basic structure of the developed mPBPK models consisted of plasma, tissue and lymph compartments.

Effects of the FcRn developmental pharmacology on the pharmacokinetics of therapeutic monoclonal IgG antibody in pediatric subjects using minimal physiologically-based pharmacokinetic modelling.

The aim of this study was to investigate neonatal Fc receptor (FcRn) concentration developmental pharmacology in adult and pediatric subjects using minimal physiologically-based pharmacokinetic (mPBPK) modelling. Three types of pharmacokinetic (PK) data for three agents (endogenous/exogenous native IgG, bevacizumab and palivizumab) were used. The adult group contained six subjects with weights from 50 to 100 kg.

Two-Pore Minimum Physiologically-based Pharmacokinetic Model to Describe the Disposition of Therapeutic Monoclonal IgG Antibody in Humans.

Purpose: The aim of this study was to develop a two-pore minimum physiologically-based pharmacokinetic (mPBPK) model in describing the pharmacokinetic (PK) of therapeutic monoclonal antibody (TMAb) in human subjects.

Methods: PK data used in this study were endogenous/exogenous native IgG and two TMAbs (palivizumab and Motavizumab-YTE) in normal volunteer or familial hypercatabolic hypoproteinemia (FIHH) patient. Several important components were implemented to overcome the limitations of the early mPBPK model, e.

Conjugation of insulin onto the sidewalls of single-walled carbon nanotubes through functionalization and diimide-activated amidation.

Purpose: The high aspect ratio of carbon nanotubes (CNTs) allows the attachment of compounds that enhance the functionality of the drug vehicle. Considering this, use of CNTs as a multifunctional insulin carrier may be an interesting prospect to explore.

Materials And Methods: The carboxylic acid groups were functionalized on the sidewalls of single-walled CNTs (SWCNTs) followed by diimidation to form amide bonds with the amine groups of the insulin.