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.

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 - July 22, 2023 Category: Drugs & Pharmacology Source Type: research

A two-stages global sensitivity analysis by using the δ sensitivity index in presence of correlated inputs: application on a tumor growth inhibition model based on the dynamic energy budget theory
AbstractGlobal sensitivity analysis (GSA) evaluates the impact of variability and/or uncertainty of the model parameters on given model outputs. GSA is useful for assessing the quality of Pharmacometric model inference. Indeed, model parameters can be affected by high (estimation) uncertainty due to the sparsity of data. Independence between model parameters is a common assumption of GSA methods. However, ignoring (known) correlations between parameters may alter model predictions and, then, GSA results. To address this issue, a novel two-stages GSA technique based on the δ index, which is well-defined also in presence of...
Source: Journal of Pharmacokinetics and Pharmacodynamics - July 9, 2023 Category: Drugs & Pharmacology Source Type: research

Classical structural identifiability methodology applied to low-dimensional dynamic systems in receptor theory
AbstractMathematical modelling has become a key tool in pharmacological analysis, towards understanding dynamics of cell signalling and quantifying ligand-receptor interactions. Ordinary differential equation (ODE) models in receptor theory may be used to parameterise such interactions using timecourse data, but attention needs to be paid to the theoretical identifiability of the parameters of interest. Identifiability analysis is an often overlooked step in many bio-modelling works. In this paper we introduce structural identifiability analysis (SIA) to the field of receptor theory by applying three classical SIA methods ...
Source: Journal of Pharmacokinetics and Pharmacodynamics - June 30, 2023 Category: Drugs & Pharmacology Source Type: research

Clinical validation of translational antibody PBPK model using tissue distribution data generated with 89Zr-immuno-PET imaging
AbstractThe main objective of this manuscript was to validate the ability of the monoclonal antibody physiologically-based pharmacokinetic (PBPK) model to predict tissue concentrations of antibodies in the human. To accomplish this goal, preclinical and clinical tissue distribution and positron emission tomography imaging data generated using zirconium-89 (89Zr) labeled antibodies were obtained from the literature. First, our previously published translational PBPK model for antibodies was expanded to describe the whole-body biodistribution of89Zr labeled antibody and the free89Zr, as well as residualization of free89Zr. S...
Source: Journal of Pharmacokinetics and Pharmacodynamics - June 29, 2023 Category: Drugs & Pharmacology Source Type: research

Assessing the performance of QSP models: biology as the driver for validation
AbstractValidation of a quantitative model is a critical step in establishing confidence in the model ’s suitability for whatever analysis it was designed. While processes for validation are well-established in the statistical sciences, the field of quantitative systems pharmacology (QSP) has taken a more piecemeal approach to defining and demonstrating validation. Although classical statistical m ethods can be used in a QSP context, proper validation of a mechanistic systems model requires a more nuanced approach to what precisely is being validated, and what role said validation plays in the larger context of the analy...
Source: Journal of Pharmacokinetics and Pharmacodynamics - June 29, 2023 Category: Drugs & Pharmacology Source Type: research

Physiologically-based pharmacokinetic modeling to predict drug-drug interaction of enzalutamide with combined P-gp and CYP3A substrates
AbstractEnzalutamide is known to strongly induce cytochrome P450 3A4 (CYP3A4). Furthermore, enzalutamide showed induction and inhibition of P-glycoprotein (P-gp) in in vitro studies. A clinical drug-drug interaction (DDI) study between enzalutamide and digoxin, a typical P-gp substrate, suggested enzalutamide has weak inhibitory effect on P-gp substrates. Direct oral anticoagulants (DOACs), such as apixaban and rivaroxaban, are dual substrates of CYP3A4 and P-gp, and hence it is recommended to avoid co-administration of these DOACs with combined P-gp and strong CYP3A inducers. Enzalutamide ’s net effect on P-gp and CYP3A...
Source: Journal of Pharmacokinetics and Pharmacodynamics - June 21, 2023 Category: Drugs & Pharmacology Source Type: research

Challenges, approaches and enablers: effectively triangulating towards dose selection in pediatric rare diseases
AbstractDose selection is an integral part of a molecule ’s journey to become medicine. On top of typical challenges faced in dose selection for more common diseases, pediatric rare disease has additional unique challenges due to the combination of ‘rare’ and ‘pediatric’ populations. Using the central theme of maximizing ‘relevant’ informati on to overcome information paucity, dose selection strategy in pediatric rare diseases is discussed using a triangulation concept involving challenges, approaches and very importantly, enablers. Using actual examples, unique scenarios are discussed where specific enablers...
Source: Journal of Pharmacokinetics and Pharmacodynamics - June 9, 2023 Category: Drugs & Pharmacology Source Type: research

Population pharmacokinetic and pharmacokinetic-pharmacodynamic modeling of bempedoic acid and low-density lipoprotein cholesterol in healthy subjects and patients with dyslipidemia
AbstractPopulation pharmacokinetics (popPK) of bempedoic acid and the popPK/pharmacodynamic (popPK/PD) relationship between bempedoic acid concentrations and serum low-density lipoprotein cholesterol (LDL-C) from baseline were characterized. A two-compartment disposition model with a transit absorption compartment and linear elimination best described bempedoic acid oral pharmacokinetics (PK). Multiple covariates, including renal function, sex, and weight, had statistically significant effects on the predicted steady-state area under the curve. Mild (estimated glomerular filtration rate (eGFR) 60 to < 90 mL/min v...
Source: Journal of Pharmacokinetics and Pharmacodynamics - May 27, 2023 Category: Drugs & Pharmacology Source Type: research