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.

Joint longitudinal model-based meta-analysis of FEV1 and exacerbation rate in randomized COPD trials
This study not only evaluated the predictability of a published MBMA for forced expiratory volume in one second (FEV1) and its link to annual exacerbation rate in patients with chronic obstructive pulmonary disease (COPD) but also included data from new RCTs. A comparative effectiveness analysis across all drugs was also performed. Aggregated level data were collected from RCTs published between July 2013 and November 2020 (n  = 132 references comprising 156 studies) and combined with data used in the legacy MBMA (published RCTs up to July 2013 - n = 142). The augmented data (n = 298) were used to evaluate the ...
Source: Journal of Pharmacokinetics and Pharmacodynamics - March 22, 2023 Category: Drugs & Pharmacology Source Type: research

Implementation of non-linear mixed effects models defined by fractional differential equations
AbstractFractional differential equations (FDEs), i.e. differential equations with derivatives of non-integer order, can describe certain experimental datasets more accurately than classic models and have found application in pharmacokinetics (PKs), but wider applicability has been hindered by the lack of appropriate software. In the present work an extension of NONMEM software is introduced, as a FORTRAN subroutine, that allows the definition of nonlinear mixed effects (NLME) models with FDEs. The new subroutine can handle arbitrary user defined linear and nonlinear models with multiple equations, and multiple doses and c...
Source: Journal of Pharmacokinetics and Pharmacodynamics - March 21, 2023 Category: Drugs & Pharmacology Source Type: research

An exploratory analysis of the performance of methylphenidate regimens based on a PKPD model of dopamine and norepinephrine transporter occupancy
AbstractMethylphenidate (MPH) is a psychostimulant which inhibits the uptake of dopamine and norepinephrine transporters, DAT and NET, and is mostly used to treat Attention Deficit/Hyperactivity Disorder. The current dose optimization is done through titration, a cumbersome approach for patients. To assess the therapeutic performance of MPH regimens, we introduce an in silico framework composed of (i) a population pharmacokinetic model of MPH, (ii) a pharmacodynamic (PD) model of DAT and NET occupancy, (iii) a therapeutic box delimited by time and DAT occupancy, and (iv) a performance score computation. DAT occupancy data ...
Source: Journal of Pharmacokinetics and Pharmacodynamics - March 17, 2023 Category: Drugs & Pharmacology Source Type: research

Comparison of sequential and joint nonlinear mixed effects modeling of tumor kinetics and survival following Durvalumab treatment in patients with metastatic urothelial carcinoma
In conclusion, joint modeling enabled the establishment of a robust association between TK and OS and may represent a better choice for parametric survival analyses over the sequential approach. (Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - March 12, 2023 Category: Drugs & Pharmacology Source Type: research

New Editorial Advisory Board Members and a Thank You
(Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - March 10, 2023 Category: Drugs & Pharmacology Source Type: research

Mechanistic incorporation of FcRn binding in plasma and endosomes in a whole body PBPK model for large molecules
This study investigates the large molecules model in PK-Sim® and its applicability to molecules with FcRn binding affinity in plasma. With this purpose, simulations of biologicals with and without plasma binding to FcRn were performed with the large molecule model in PK-Sim®. Subsequently, this model was extended to ensure a more mechanistic description of the internalisation of FcRn and the FcRn-drug complexes. Finally, the newly developed model was used in simulations to explore the sensitivity for FcRn binding in the plasma space, and it was fitted to an in vivo dataset of wild-type IgG and FcRn inhibitor plasma conce...
Source: Journal of Pharmacokinetics and Pharmacodynamics - March 6, 2023 Category: Drugs & Pharmacology Source Type: research

A comprehensive regulatory and industry review of modeling and simulation practices in oncology clinical drug development
AbstractExposure –response (E–R) analyses are an integral component in the development of oncology products. Characterizing the relationship between drug exposure metrics and response allows the sponsor to use modeling and simulation to address both internal and external drug development questions (e.g., optimal dose, frequency of administration, dose adjustments for special populations). This white paper is the output of an industry-government collaboration among scientists with broad experience in E–R modeling as part of regulatory submissions. The goal of this white paper is to provide guidance on wha t the prefer...
Source: Journal of Pharmacokinetics and Pharmacodynamics - March 4, 2023 Category: Drugs & Pharmacology Source Type: research

Correction to: Characterization of exposure –Clinical Dementia Rating–Sum of Boxes relationship in subjects with early Alzheimer’s disease from the aducanumab Phase 3 trials
(Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - March 4, 2023 Category: Drugs & Pharmacology Source Type: research

A comprehensive regulatory and industry review of modeling and simulation practices in oncology clinical drug development
AbstractExposure –response (E–R) analyses are an integral component in the development of oncology products. Characterizing the relationship between drug exposure metrics and response allows the sponsor to use modeling and simulation to address both internal and external drug development questions (e.g., optimal dose, frequency of administration, dose adjustments for special populations). This white paper is the output of an industry-government collaboration among scientists with broad experience in E–R modeling as part of regulatory submissions. The goal of this white paper is to provide guidance on wha t the prefer...
Source: Journal of Pharmacokinetics and Pharmacodynamics - March 4, 2023 Category: Drugs & Pharmacology Source Type: research