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.

Optimal sample selection applied to information rich, dense data
AbstractDense data can be classified into superdense information-poor data (type 1 dense data) and dense information-rich data (type 2 dense data). Arbitrary, random, or optimal thinning may be applied to type 1 dense data to minimise computational burden and statistical issues (such as autocorrelation). In contrast, a prospective or retrospective optimal design can be applied to type 2 dense data to maximise information gain from limited resources (capital and/or time). Here we describe a retrospective optimal selection strategy for quantification of unbound drug concentration from a discrete set of plasma samples where t...
Source: Journal of Pharmacokinetics and Pharmacodynamics - August 10, 2023 Category: Drugs & Pharmacology Source Type: research

Translational physiologically-based pharmacokinetic model for ocular disposition of monoclonal antibodies
AbstractWe have previously published a PBPK model comprising the ocular compartment to characterize the disposition of monoclonal antibodies (mAbs) in rabbits. While rabbits are commonly used preclinical species in ocular research, non-human primates (NHPs) have the most phylogenetic resemblance to humans including the presence of macula in the eyes as well as higher sequence homology. However, their use in ocular research is limited due to the strict ethical guidelines. Similarly, in humans the ocular samples cannot be collected except for the tapping of aqueous humor (AH). Therefore, we have translated this rabbit model ...
Source: Journal of Pharmacokinetics and Pharmacodynamics - August 9, 2023 Category: Drugs & Pharmacology Source Type: research

Population pharmacokinetic modeling and dosing simulation of avalglucosidase alfa for selecting alternative dosing regimen in pediatric patients with late-onset pompe disease
AbstractAvalglucosidase alfa (AVAL) was approved in the United States (2021) for patients with late-onset Pompe disease (LOPD), aged  ≥ 1 year. In the present study, pharmacokinetic (PK) simulations were conducted to propose alternative dosing regimens for pediatric LOPD patients based on a bodyweight cut-off. Population PK (PopPK) analysis was performed using nonlinear mixed effect modeling approach on pooled data from thr ee clinical trials with LOPD patients, and a phase 2 study (NCT03019406) with infantile-onset Pompe disease (IOPD: 1–12 years) patients. A total of 2257 concentration-time points from 91 patient...
Source: Journal of Pharmacokinetics and Pharmacodynamics - August 3, 2023 Category: Drugs & Pharmacology Source Type: research

International society of Pharmacometrics Mentorship Program (IMP): feedback survey from the first cohort of mentor-mentee pairs
AbstractThe International Society of Pharmacometrics (ISoP) Mentorship Program (IMP) aims to help professionals at all career stages to transition into the pharmacometrics field, move to a different role/area within pharmacometrics, or expand their skillsets. The program connects mentees at various stages of their careers with mentors based on established criteria for mentor-mentee matching. Pairing mentees with appropriate mentors ensures strong alignment between mentees ’ interests and mentors’ expertise as this is critical to the success and continuation of the relationship between the mentor and mentee. Once mentor...
Source: Journal of Pharmacokinetics and Pharmacodynamics - August 1, 2023 Category: Drugs & Pharmacology Source Type: research

Computational neurosciences and quantitative systems pharmacology: a powerful combination for supporting drug development in neurodegenerative diseases
AbstractSuccessful clinical development of new therapeutic interventions is notoriously difficult, especially in neurodegenerative diseases, where predictive biomarkers are scarce and functional improvement is often based on patient ’s perception, captured by structured interviews. As a consequence, mechanistic modeling of the processes relevant to therapeutic interventions in CNS disorders has been lagging behind other disease indications, probably because of the perceived complexity of the brain. However in this report, we develop the argument that a combination of Computational Neurosciences and Quantitative Systems P...
Source: Journal of Pharmacokinetics and Pharmacodynamics - July 28, 2023 Category: Drugs & Pharmacology Source Type: research

Go beyond the limits of genetic algorithm in daily covariate selection practice
AbstractCovariate identification is an important step in the development of a population pharmacokinetic/pharmacodynamic model. Among the different available approaches, the stepwise covariate model (SCM) is the most used.However, SCM is based on a local search strategy, in which the model-building process iteratively tests the addition or elimination of a single covariate at a time given all the others. This introduces a heuristic to limit the searching space and then the computational complexity, but, at the same time, can lead to a suboptimal solution. The application of genetic algorithms (GAs) for covariate selection ...
Source: Journal of Pharmacokinetics and Pharmacodynamics - July 26, 2023 Category: Drugs & Pharmacology Source Type: research

Correction to: Classical structural identifiability methodology applied to low-dimensional dynamic systems in receptor theory
(Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - July 26, 2023 Category: Drugs & Pharmacology Source Type: research

Go beyond the limits of genetic algorithm in daily covariate selection practice
AbstractCovariate identification is an important step in the development of a population pharmacokinetic/pharmacodynamic model. Among the different available approaches, the stepwise covariate model (SCM) is the most used.However, SCM is based on a local search strategy, in which the model-building process iteratively tests the addition or elimination of a single covariate at a time given all the others. This introduces a heuristic to limit the searching space and then the computational complexity, but, at the same time, can lead to a suboptimal solution. The application of genetic algorithms (GAs) for covariate selection ...
Source: Journal of Pharmacokinetics and Pharmacodynamics - July 26, 2023 Category: Drugs & Pharmacology Source Type: research

Generation and application of avatars in pharmacometric modelling
AbstractSimulations from population models have critical applications in drug discovery and development. Avatars or digital twins, defined as individual simulations matching clinical criteria of interest compared to observations from a real subject within a predefined margin of accuracy, may be a better option for simulations performed to inform future drug development stages in cases where an adequate model is not achievable. The aim of this work was to (1) investigate methods for generating avatars with pharmacometric models, and (2) explore the properties of the generated avatars to assess the impact of the different se...
Source: Journal of Pharmacokinetics and Pharmacodynamics - July 24, 2023 Category: Drugs & Pharmacology Source Type: research