Balaji Agoram

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Erythropoietin (EPO) receptor-mediated endocytosis and degradation in the bone marrow has been hypothesized to be the major clearance pathway of erythropoiesis-stimulating agents (ESA). We investigated the role of this pathway in ESA clearance by determining the pharmacokinetic profiles after intravenous (IV) dosing in rats and mice of recombinant human EPO(More)
AIM To develop and evaluate a population pharmacokinetic (PK) model of the long-acting erythropoiesis-stimulating protein, darbepoetin alfa in healthy subjects. METHODS PK profiles were obtained from 140 healthy subjects receiving single intravenous and/or single or multiple subcutaneous doses of darbepoetin alfa (0.75-8.0 microg kg(-1), or either 80 or(More)
We consider the relationship between the target affinity of a monoclonal antibody and its in vivo potency. The dynamics of the system is described mathematically by a target-mediated drug disposition model. As a measure of potency, we consider the minimum level of the free receptor following a single bolus injection of the ligand into the plasma(More)
Quantitative and systems pharmacology (QSP) is an emerging modelling technique that combines the flexibility of systems biology and tractability of compartmental pharmacokinetic-pharmacodynamic modelling techniques. Historically, there has been extensive use of QSP within the field of pharmacokinetics to optimise drug biopharmaceutical properties. However,(More)
Recent clinical studies suggest sustained treatment effects of interleukin-1β (IL-1β)-blocking therapies in type 2 diabetes mellitus. The underlying mechanisms of these effects, however, remain underexplored. Using a quantitative systems pharmacology modeling approach, we combined ex vivo data of IL-1β effects on β-cell function and turnover with a disease(More)
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Recent regulatory guidance has highlighted the importance of using pharmacokinetic-pharmacodynamic (PK-PD) modelling in the selection of starting doses in first-in-human trials of high-risk biologics. However, limited examples exist in literature illustrating this procedure. WHAT THIS STUDY ADDS An interpretation(More)
  • B Agoram
  • CPT: pharmacometrics & systems pharmacology
  • 2014
Based on the author's recent experience, there appears to be some confusion regarding the steps required to qualify a systems pharmacology model as adequate for the intended purpose. This manuscript outlines the model evaluation approach used in the author's recent publication(1) on the systems pharmacology of a 5-lipoxygenase inhibitor and is an attempt to(More)
Collagen mechanics are crucial to the function and dysfunction of many tissues, including blood vessels and articular cartilage, and bioartificial tissues. Previous attempts to develop computer simulations of collagenous tissue based on macroscopic property descriptions have often been limited in application by the simplicity of the model; simulations based(More)
In patients with chronic heart failure (CHF), anemia is associated with more severe symptoms and worse prognosis. Erythropoiesis-stimulating proteins (ESPs) increase hemoglobin and may be of therapeutic benefit. We investigated the pharmacokinetics and pharmacodynamics of the long-acting ESP, darbepoetin alfa, administered on 2 occasions 1 month apart to 30(More)
AIMS Tralokinumab, an investigational human immunoglobulin G4 monoclonal antibody, potently and specifically neutralizes interleukin-13, a central mediator of asthma. Tralokinumab has shown improvements in clinical endpoints in adults with uncontrolled asthma. The present study explored the pharmacokinetics (PK) and safety of a single tralokinumab dose, and(More)