Journal of Pharmacokinetics and Pharmacodynamics This 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.

Subgroup identification-based model selection to improve the predictive performance of individualized dosing
AbstractCurrently, model-informed precision dosing uses one population pharmacokinetic model that best fits the target population. We aimed to develop a subgroup identification-based model selection approach to improve the predictive performance of individualized dosing, using vancomycin in neonates/infants as a test case. Data from neonates/infants with at least one vancomycin concentration was randomly divided into training and test dataset. Population predictions from published vancomycin population pharmacokinetic models were calculated. The single best-performing model based on various performance metrics, including m...
Source: Journal of Pharmacokinetics and Pharmacodynamics - February 24, 2024 Category: Drugs & Pharmacology Source Type: research

A minimal physiologically based pharmacokinetic model to study the combined effect of antibody size, charge, and binding affinity to FcRn/antigen on antibody pharmacokinetics
AbstractProtein therapeutics have revolutionized the treatment of a wide range of diseases. While they have distinct physicochemical characteristics that influence their absorption, distribution, metabolism, and excretion (ADME) properties, the relationship between the physicochemical properties and PK is still largely unknown. In this work we present a minimal physiologically-based pharmacokinetic (mPBPK) model that incorporates a multivariate quantitative relation between a therapeutic ’s physicochemical parameters and its corresponding ADME properties. The model’s compound-specific input includes molecular weight, m...
Source: Journal of Pharmacokinetics and Pharmacodynamics - February 24, 2024 Category: Drugs & Pharmacology Source Type: research

Thoughts on plagiarism and the case against Claudine Gay
(Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - February 15, 2024 Category: Drugs & Pharmacology Source Type: research

Population pharmacokinetics of the dual endothelin receptor antagonist aprocitentan in subjects with or without essential or resistant hypertension
AbstractAprocitentan is a novel, potent, dual endothelin receptor antagonist that recently demonstrated efficacy in the treatment of difficult-to-treat (resistant) hypertension. The aim of this study was to develop a population pharmacokinetic (PK) model describing aprocitentan plasma concentration over time, to investigate relationships between subject-specific factors (covariates) and model parameters, and to quantify the influence of the identified covariates on the exposure to aprocitentan via model-based simulations, enabling judgment about the clinical relevance of the covariates.PK data from 902 subjects in ten Phas...
Source: Journal of Pharmacokinetics and Pharmacodynamics - February 8, 2024 Category: Drugs & Pharmacology Source Type: research

A population pharmacokinetics model of balovaptan to support dose selection in adult and pediatric populations
AbstractBalovaptan is a brain-penetrating vasopressin receptor 1a antagonist previously investigated for the core symptoms of autism spectrum disorder (ASD). A population pharmacokinetic (PK) model of balovaptan was developed, initially to assist clinical dosing for adult and pediatric ASD studies and subsequently for new clinical indications including malignant cerebral edema (MCE) and post-traumatic stress disorder. The final model incorporates one-compartment disposition and describes time- and dose-dependent non-linear PK through empirical drug binding and a gut extraction component with turnover. An age effect on clea...
Source: Journal of Pharmacokinetics and Pharmacodynamics - February 3, 2024 Category: Drugs & Pharmacology Source Type: research

Correction: External control arms for rare diseases: building a body of supporting evidence
(Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - January 19, 2024 Category: Drugs & Pharmacology Source Type: research

How drug onset rate and duration of action affect drug forgiveness
AbstractMedication nonadherence is one of the largest problems in healthcare today, particularly for patients undergoing long-term pharmacotherapy. To combat nonadherence, it is often recommended to prescribe so-called “forgiving” drugs, which maintain their effect despite lapses in patient adherence. Nevertheless, drug forgiveness is difficult to quantify and compare between different drugs. In this paper, we construct and analyze a stochastic pharmacokinetic/pharmacodynamic (PK/PD) model to quantify and unde rstand drug forgiveness. The model parameterizes a medication merely by an effective rate of onset of effect w...
Source: Journal of Pharmacokinetics and Pharmacodynamics - January 10, 2024 Category: Drugs & Pharmacology Source Type: research

Semi-mechanistic modeling of resistance development to β-lactam and β-lactamase-inhibitor combinations
This study used semi-mechanistic mathematical modeling in combination with antibiotic sensitivity assays to assess the potential impact of different resistance mechanisms during the development of PIP-TAZ resistance in aKlebsiella pneumoniae isolate expressing CTX-M-15 and SHV-1 β-lactamases. The mathematical models were used to evaluate the potential impact of several cellular changes as a sole mediator of PIP-TAZ resistance. Our semi-mechanistic model identified 2 out of the 13 inspected mechanisms as key resistance mechanisms that may independently support the observed magnitude of PIP-TAZ resistance, namely porin loss...
Source: Journal of Pharmacokinetics and Pharmacodynamics - November 26, 2023 Category: Drugs & Pharmacology Source Type: research