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.

Global sensitivity analysis in physiologically-based pharmacokinetic/pharmacodynamic models of inhaled and opioids anesthetics and its application to generate virtual populations
AbstractThe integration between physiologically-based pharmacokinetics (PBPK) models and pharmacodynamics (PD) models makes it possible to describe the absorption, distribution, metabolism and excretion processes of drugs, together with the concentration –response relationship, being a fundamental framework with wide applications in pharmacology. Nevertheless, the enormous complexity of PBPK models and the large number of parameters that define them leads to the need to study and understand how the uncertainty of the parameters affects the variabi lity of the models output. To study this issue, this paper proposes a glob...
Source: Journal of Pharmacokinetics and Pharmacodynamics - May 26, 2022 Category: Drugs & Pharmacology Source Type: research

Knowledge dissemination and central indexing of resources in pharmacometrics: an ISOP education working group initiative
AbstractPharmacometrics is a constantly evolving field that plays a major role in decision making in drug development and clinical monitoring. Scientists in Pharmacometrics, especially in their early phases of career, are often faced with the challenge of identifying adequate resources for self-training and education. Hence, the ISoP Education Committee through its working group dedicated to Central Indexing and knowledge Dissemination has built a database of worldwide educational programs and most common references in Pharmacometrics. (Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - April 26, 2022 Category: Drugs & Pharmacology Source Type: research

Application of machine learning based methods in exposure –response analysis
AbstractRobust estimation of exposure response analysis relies on correct specification of the model structure with traditional parametric approach. However, the assumptions of the handcrafted model may not always hold or verifiable. Here, we conducted a simulation study to assess the performance of machine learning-based techniques in exposure –response (E–R) analysis where data were generated by a complicated nonlinear system under one dose level. Two analysis options involving machine learning were evaluated. The first option was based on marginal structural model with inverse probability weighting, where machine le...
Source: Journal of Pharmacokinetics and Pharmacodynamics - March 11, 2022 Category: Drugs & Pharmacology Source Type: research

Integrated multiple analytes and semi-mechanistic population pharmacokinetic model of tusamitamab ravtansine, a DM4 anti-CEACAM5 antibody-drug conjugate
AbstractTusamitamab ravtansine (SAR408701) is an antibody-drug conjugate (ADC), combining a humanized monoclonal antibody (IgG1) targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and a potent cytotoxic maytansinoid derivative, DM4, inhibiting microtubule assembly. SAR408701 is currently in clinical development for the treatment of advanced solid tumors expressing CEACAM5. It is administered intravenously as a conjugated antibody with an average Drug Antibody Ratio (DAR) of 3.8. During SAR408701 clinical development, four entities were measured in plasma: conjugated antibody (SAR408701), naked an...
Source: Journal of Pharmacokinetics and Pharmacodynamics - February 15, 2022 Category: Drugs & Pharmacology Source Type: research

A pharmacokinetic and pharmacodynamic analysis of drug forgiveness
AbstractNonadherence to medication is a major public health problem. To combat nonadherence, some clinicians have suggested using “forgiving” drugs, which maintain efficacy in spite of delayed or missed doses. What pharmacokinetic (PK) and pharmacodynamic (PD) factors make a drug forgiving? In this paper, we address this question by analyzing a linear PK/PD model for a patient with imperfect adherence. We assume that the d rug effect is far from maximal and consider direct effect, effect compartment (biophase), and indirect response PD models. We prove that the average drug effect relative to the clinically desired eff...
Source: Journal of Pharmacokinetics and Pharmacodynamics - February 13, 2022 Category: Drugs & Pharmacology Source Type: research

Correction to: R-praziquantel integrated population pharmacokinetics in preschool- and school-aged African children infected with Schistosoma  mansoni and S. haematobium and Lao adults infected with Opisthorchis viverrini
(Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - February 4, 2022 Category: Drugs & Pharmacology Source Type: research

Two heads are better than one: current landscape of integrating QSP and machine learning
AbstractQuantitative systems pharmacology (QSP) modeling is applied to address essential questions in drug development, such as the mechanism of action of a therapeutic agent and the progression of disease. Meanwhile, machine learning (ML) approaches also contribute to answering these questions via the analysis of multi-layer ‘omics’ data such as gene expression, proteomics, metabolomics, and high-throughput imaging. Furthermore, ML approaches can also be applied to aspects of QSP modeling. Both approaches are powerful tools and there is considerable interest in integrating QSP modeling and ML. So far, a few successf u...
Source: Journal of Pharmacokinetics and Pharmacodynamics - February 1, 2022 Category: Drugs & Pharmacology Source Type: research