Journal of Pharmacokinetics and Pharmacodynamics 
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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.Latent variable indirect response modeling of clinical efficacy endpoints with combination therapy: application to guselkumab and golimumab in patients with ulcerative colitis
This study aims to demonstrate that the latent variable IDR approach provides a convenient longitudinal exposure-response modeling framework to assess potential interaction effects of combination therapies. This is illustrated by an application to the exposure-response modeling of guselkumab, a monoclonal antibody in clinical development that blocks the interleukin-23p19 subunit, and golimumab, a monoclonal antibody that binds with high affinity to tumor necrosis factor-alpha. A Phase 2a study was conducted in 214 patients with moderate-to severe active ulcerative colitis for which longitudinal assessments of disease sever...
Source: Journal of Pharmacokinetics and Pharmacodynamics - January 17, 2023 Category: Drugs & Pharmacology Source Type: research
Investigating the contribution of residual unexplained variability components on bias and imprecision of parameter estimates in population pharmacokinetic mixed-effects modeling
AbstractIn a nonlinear mixed-effects modeling (NLMEM) approach of pharmacokinetic (PK) and pharmacodynamic (PD) data, two levels of random effects are generally modeled: between-subject variability (BSV) and residual unexplained variability (RUV). The goal of this simulation-estimation study was to investigate the extent to which PK and RUV model misspecification, errors in recording dosing and sampling times, and variability in drug content uniformity contribute to the estimated magnitude of RUV and PK parameter bias. A two-compartment model with first-order absorption and linear elimination was simulated as a true model....
Source: Journal of Pharmacokinetics and Pharmacodynamics - January 8, 2023 Category: Drugs & Pharmacology Source Type: research
Characterization of exposure –Clinical Dementia Rating–Sum of Boxes relationship in subjects with early Alzheimer’s disease from the aducanumab Phase 3 trials
AbstractClinical Dementia Rating –Sum of Boxes (CDR–SB) assessments from two Phase 3 studies (ENGAGE and EMERGE) of aducanumab in subjects with early Alzheimer’s disease (AD) were pooled to develop an exposure–response (ER) model. A linear model in the logit-transformed scaled CDR–SB best characterized the time profile fo r placebo- and aducanumab-treated subjects, with concentration as the exposure metric. The model allowed delineation of slow (4%), typical (86%), and fast (10%) progressing subpopulations in the data. The estimated drug effect on the disease progression rate was significant, 2.05 L/(g·year), wi...
Source: Journal of Pharmacokinetics and Pharmacodynamics - January 4, 2023 Category: Drugs & Pharmacology Source Type: research
Generative models for age, race/ethnicity, and disease state dependence of physiological determinants of drug dosing
AbstractDosing requires consideration of diverse patient-specific factors affecting drug pharmacokinetics and pharmacodynamics. The available pharmacometric methods have limited capacity for modeling the inter-relationships and patterns of variability among physiological determinants of drug dosing (PDODD). To investigate whether generative adversarial networks (GANs) can learn a generative model from real-world data that recapitulates PDODD distributions. A GAN architecture was developed for modeling a PDODD panel comprised of: age, sex, race/ethnicity, body weight, body surface area, total body fat, lean body weight, alb...
Source: Journal of Pharmacokinetics and Pharmacodynamics - December 24, 2022 Category: Drugs & Pharmacology Source Type: research
Population pharmacokinetic and pharmacodynamic model of propofol externally validated in Korean elderly subjects
AbstractThe Eleveld propofol pharmacokinetic (PK) model, which was developed based on a broad range of populations, showed greater bias ( − 27%) in elderly subjects in a previous validation study conducted by Vellinga and colleagues. We aimed to develop and externally validate a new PK-pharmacodynamic (PK-PD) model of propofol for elderly subjects. A population PK-PD model was constructed using propofol plasma concentrations and b ispectral index (BIS) values that were obtained from 31 subjects aged 65 years older in previously published phase I studies. The predictive performance of the newly-developed PK-PD model (C...
Source: Journal of Pharmacokinetics and Pharmacodynamics - December 16, 2022 Category: Drugs & Pharmacology Source Type: research
Convolution-based approach for modeling the paliperidone extended release and Long-Acting Injectable (LAI) PK of once-, and three-monthly products administration and for optimizing the development of new LAI products
AbstractThe aim of this paper was to develop a convolution-based modeling approach for describing the paliperidone PK resulting from the administration of extended-release once-a-day oral dose, and once- and three monthly long-acting injectable products and to compare the performances of this approach to the traditional modeling strategy. The results of the analyses indicated that the traditional and convolution-based models showed comparable performances in the characterization of the paliperidone PK. However, the convolution-based approach showed several appealing features that justify the choice of this modeling as a ...
Source: Journal of Pharmacokinetics and Pharmacodynamics - December 9, 2022 Category: Drugs & Pharmacology Source Type: research
Two compartmental fractional derivative model with general fractional derivative
This study presents a new two compartmental model with, recently defined General fractional derivative. We review that concept of General fractional derivative and use the kernel function that generalizes the classical Caputo derivative in a mathematically consistent way. Next we use this model to study the release of antibiotic gentamicin in poly (vinyl alcohol)/gentamicin(PVA/Gent) hydrogel aimed for wound dressing in medical treatment of deep chronical wounds. The PVA/Gent hydrogel was prepared by physical cross linking of poly (vinyl alcohol) dispersion using freezing –thawing method, and then was swollen in gentamic...
Source: Journal of Pharmacokinetics and Pharmacodynamics - December 8, 2022 Category: Drugs & Pharmacology Source Type: research
