Leonid Gibiansky

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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)
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)
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)
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)
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)
Tocilizumab is a recombinant humanized antihuman interleukin-6 receptor monoclonal antibody, which inhibits binding of IL-6 to its soluble (sIL-6R) and membrane-expressed (mIL-6R) receptors. The work investigated whether the observed decline in peripheral neutrophil and platelet counts after tocilizumab administration can be directly explained by(More)
Sharp bounds on the effective thermal expansion coefficients of isotropic multiphase composites and isotropic polycrystals are obtained by using classical variational principles and the translation method. Our bounds are appreciably narrower than the known Schapery-Rosen-Hashin bounds. Conditions are formulated that guarantee a one-to-one correspondence(More)
Placebo and pharmacodynamic (PD) models were developed which link temporal measures of efficacy in children with attention deficit hyperactivity disorder (ADHD) and methylphenidate (MPH) plasma concentrations from adults. These models can be used to predict daily pediatric clinical measure profiles following administration of different MPH formulations in(More)
This work proposes and evaluates two methods (CM1 and CM2) for detecting non-compliance using concentration–time data and for obtaining estimates of population pharmacokinetic model parameters in a population with prevalent non-compliance. CM1 estimates individual residual variability (RV) and identifies subjects with higher than average RV as(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)