Journal of Pharmacokinetics and Pharmacodynamics Journal of Pharmacokinetics and Pharmacodynamics RSS feedThis is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Analysis of cellular kinetic models suggest that physiologically based model parameters may be inherently, practically unidentifiable
AbstractPhysiologically-based pharmacokinetic and cellular kinetic models are used extensively to predict concentration profiles of drugs or adoptively transferred cells in patients and laboratory animals. Models are fit to data by the numerical optimisation of appropriate parameter values. When quantities such as the area under the curve are all that is desired, only a close qualitative fit to data is required. When the biological interpretation of the model that produced the fit is important, an assessment of uncertainties is often also warranted. Often, a goal of fitting PBPK models to data is to estimate parameter valu...
Source: Journal of Pharmacokinetics and Pharmacodynamics - August 6, 2022 Category: Drugs & Pharmacology Source Type: research

Variability and uncertainty: interpretation and usage of pharmacometric simulations and intervals
AbstractVariability and estimation uncertainty are important sources of variation in pharmacometric simulations. Different combinations of uncertainty and the variability components lead to a variety types of simulation intervals, and many realized and unrealized confusions exist among pharmacometricians on their interpretation and usage. This commentary aims to clarify some of the important underlying concepts and provide a convenient guideline on pharmacometric simulation conduct and interpretation. (Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - August 4, 2022 Category: Drugs & Pharmacology Source Type: research

Estimation of time to progression and post progression survival using joint modeling of summary level OS and PFS data with an ordinary differential equation model
AbstractSummary measures such as progression-free survival (PFS) and overall survival (OS) are commonly reported in literature for oncology trials, while time to progression (TTP) and post progression survival (PPS) are not usually reported. A time-variant transition hazard model was developed using an ordinary differential equation (ODE) model to estimate TTP and PPS from summary level PFS and OS. The model was applied to published data from immune checkpoint inhibitor trials for non-small cell lung cancer (NSCLC) in a meta-analysis framework. This model-based method was able to robustly estimate TTP and PPS from summary ...
Source: Journal of Pharmacokinetics and Pharmacodynamics - July 23, 2022 Category: Drugs & Pharmacology Source Type: research

Development of minimal physiologically-based pharmacokinetic-pharmacodynamic models for characterizing cellular kinetics of CAR T cells following local deliveries in mice
In this study, we established mouse minimal physiologically-based pharmacokinetic (mPBPK) models combined with pharmacodynamic (PD) components to delineate CAR T cell distribution, proliferation, tumor growth, and tumor cell killing in the cases of pleural and liver tumors. The pleural tumor model reasonably captured published CAR T cellular kinetic and tumor growth profiles in mice. The mPBPK-PD simulation of a liver tumor mouse model showed a substantial increase in initial tumor infiltration and earlier CAR T cell proliferation with local hepatic artery delivery compared to portal vein and intravenous (i.v.) injections ...
Source: Journal of Pharmacokinetics and Pharmacodynamics - July 22, 2022 Category: Drugs & Pharmacology Source Type: research

Application of different approaches to generate virtual patient populations for the quantitative systems pharmacology model of erythropoiesis
AbstractIn a standard situation, a quantitative systems pharmacology model describes a “reference patient,” and the model parameters are fixed values allowing only the mean values to be described. However, the results of clinical trials include a description of variability in patients’ responses to a drug, which is typically expressed in terms of conventional statistical paramet ers, such as standard deviations (SDs) from mean values. Therefore, in this study, we propose and compare four different approaches: (1) Monte Carlo Markov Chain (MCMC); (2) model fitting to Monte Carlo sample; (3) population of clones; (4) s...
Source: Journal of Pharmacokinetics and Pharmacodynamics - July 7, 2022 Category: Drugs & Pharmacology Source Type: research

Exploring Inductive Linearization for simulation and estimation with an application to the Michaelis –Menten model
This study explores the properties ofInductive Linearization when coupled with EVD for integration of the LTV ODE and illustrates how the efficiency of the method can be improved. Improvements were based on three approaches, (1) incorporation of a convergence criterion for the iterative linearization process (for simulation and estimation), (2) creating more efficient step sizes for EVD (for simulation and estimation), and (3) updating the initial conditions of theInductive Linearization (for estimation). The performance of these improvements were evaluated using single subject stochastic simulation-estimation with an appl...
Source: Journal of Pharmacokinetics and Pharmacodynamics - July 5, 2022 Category: Drugs & Pharmacology Source Type: research

A quantitative systems pharmacology model of plasma potassium regulation by the kidney and aldosterone
AbstractPlasma potassium regulation within a narrow range is vital for life. The risk for hyperkalemia increases when kidney function is impaired and with therapeutic interventions such as mineralocorticoid receptor antagonists (MRAs). The kidney maintains potassium homeostasis by matching potassium intake and excretion, in part through the action of aldosterone. A mechanistic mathematical model was developed and used to investigate the effect of renal impairment and MRAs on plasma potassium levels. The model describes renal potassium filtration, reabsorption, and secretion along the nephron; potassium-aldosterone regulato...
Source: Journal of Pharmacokinetics and Pharmacodynamics - July 1, 2022 Category: Drugs & Pharmacology Source Type: research

Should patients skip late doses of medication? A pharmacokinetic perspective
AbstractMissed doses, late doses, and other dosing irregularities are major barriers to effective pharmacotherapy, especially for the treatment of chronic conditions. What should a patient do if they did not take their last dose at the prescribed time? Should they take it late or skip it? In this paper, we investigate the pharmacokinetic effects of taking a late dose. We consider a single compartment model with linear absorption and elimination for a patient instructed to take doses at regular time intervals. We suppose that the patient forgets to take a dose and then realizes some time later and must decide what remedial ...
Source: Journal of Pharmacokinetics and Pharmacodynamics - June 20, 2022 Category: Drugs & Pharmacology Source Type: research