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Models for drugs exhibiting target-mediated drug disposition (TMDD) play an important role in the investigation of biological products (Mager and Jusko 2001). These models are often overparameterized and difficult to converge. A simpler quasi-equilibrium (QE) approximation of the general model has been suggested (Mager and Krzyzanski 2005), but even this(More)
Until recently, most therapeutic monoclonal antibodies (mAb) were designed to bind only one target. However, several existing mAbs bind to soluble and membrane forms of the same receptor. Moreover, design of bi-specific and multi-specific proteins that bind to more than one target is a promising direction of drug design. The pharmacokinetics and(More)
PURPOSE For AMG 317, a fully human monoclonal antibody to interleukin receptor IL-4Rα, we developed a population pharmacokinetic (PK) model by fitting data from four early phase clinical trials of intravenous and subcutaneous (SC) routes simultaneously, investigated important PK covariates, and explored the relationship between exposure and IgE response. (More)
Antibody–drug conjugate (ADC) is a complex structure composed of an antibody linked to several molecules of a biologically active cytotoxic drug. The number of ADC compounds in clinical development now exceeds 30, with two of them already on the market. However, there is no rigorous mechanistic model that describes pharmacokinetic (PK) properties of these(More)
Models for drugs exhibiting target-mediated drug disposition (TMDD) describe biological processes in which drug-target binding significantly influences both pharmacodynamics (PD) and pharmacokinetics (PK). TMDD models are often over-parameterized and their parameters are difficult to estimate based on available data. Approximations of the general model have(More)
This work characterizes the pharmacokinetics (PK) of oseltamivir phosphate (OP) and its active metabolite, oseltamivir carboxylate (OC), and investigates oseltamivir i.v. dosing regimens for treatment of influenza in patients with normal renal function and with various degrees of renal impairment. Initially, data collected from 149 subjects with normal(More)
Infants are at increased risk for morbidity and mortality due to influenza. Until recently, few data were available with which to optimize oseltamivir dosing in this high-risk population. Here, data for 133 infants were pooled from two prospective pharmacokinetic/pharmacodynamic safety studies to develop a population pharmacokinetic model. A(More)
Treatment regimens involving obinutuzumab (GA101) demonstrated increased efficacy to rituximab in clinical trials for non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). However, the pharmacokinetic (PK) properties and the exposure-response relationships of obinutuzumab still need to be fully described. Data from four clinical trials of(More)
The paper compares performance of Nonmem estimation methods—first order conditional estimation with interaction (FOCEI), iterative two stage (ITS), Monte Carlo importance sampling (IMP), importance sampling assisted by mode a posteriori (IMPMAP), stochastic approximation expectation–maximization (SAEM), and Markov chain Monte Carlo Bayesian (BAYES), on the(More)
Elevated basal concentrations of glucagon and reduced postprandial glucagon suppression are partly responsible for the increased hepatic glucose production seen in type 2 diabetic patients. Recently, it was demonstrated that an antagonistic human monoclonal antibody (mAb) blocking glucagon receptor (GCGR) has profound glucose-lowering effects in various(More)