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.

Prospective approaches to gene therapy computational modeling – spotlight on viral gene therapy
AbstractClinical studies have found there still exists a lack of gene therapy dose-toxicity and dose-efficacy data that causes gene therapy dose selection to remain elusive. Model informed drug development (MIDD) has become a standard tool implemented throughout the discovery, development, and approval of pharmaceutical therapies, and has the potential to inform dose-toxicity and dose-efficacy relationships to support gene therapy dose selection. Despite this potential, MIDD approaches for gene therapy remain immature and require standardization to be useful for gene therapy clinical programs. With the goal to advance MIDD...
Source: Journal of Pharmacokinetics and Pharmacodynamics - October 17, 2023 Category: Drugs & Pharmacology Source Type: research

Low-dimensional neural ODEs and their application in pharmacokinetics
AbstractMachine Learning (ML) is a fast-evolving field, integrated in many of today ’s scientific disciplines. With the recent development of neural ordinary differential equations (NODEs), ML provides a new tool to model dynamical systems in the field of pharmacology and pharmacometrics, such as pharmacokinetics (PK) or pharmacodynamics. The novel and conceptionally different ap proach of NODEs compared to classical PK modeling creates challenges but also provides opportunities for its application. In this manuscript, we introduce the functionality of NODEs and develop specific low-dimensional NODE structures based on P...
Source: Journal of Pharmacokinetics and Pharmacodynamics - October 14, 2023 Category: Drugs & Pharmacology Source Type: research

Towards a platform quantitative systems pharmacology (QSP) model for preclinical to clinical translation of antibody drug conjugates (ADCs)
In conclusion, the presented model is a step toward a platform QSP model and strategy for ADCs, integrating multiple types of data and knowledge to predict ADC efficacy. The model has potential applicatio n to facilitate ADC design, lead candidate selection, and clinical dosing schedule optimization. (Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - October 3, 2023 Category: Drugs & Pharmacology Source Type: research

Correction to: Training the next generation of pharmacometric modelers: a multisector perspective
(Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - September 5, 2023 Category: Drugs & Pharmacology Source Type: research

Physiologically based pharmacokinetic model to predict drug –drug interactions with the antibody–drug conjugate enfortumab vedotin
AbstractEnfortumab vedotin is an antibody –drug conjugate (ADC) comprised of a Nectin-4–directed antibody and monomethyl auristatin E (MMAE), which is primarily eliminated through P-glycoprotein (P-gp)–mediated excretion and cytochrome P450 3A4 (CYP3A4)–mediated metabolism. A physiologically based pharmacokinetic (PBPK) model was de veloped to predict effects of combined P-gp with CYP3A4 inhibitor/inducer (ketoconazole/rifampin) on MMAE exposure when coadministered with enfortumab vedotin and study enfortumab vedotin with CYP3A4 (midazolam) and P-gp (digoxin) substrate exposure. A PBPK model was built for enfortuma...
Source: Journal of Pharmacokinetics and Pharmacodynamics - August 26, 2023 Category: Drugs & Pharmacology Source Type: research

Training the next generation of pharmacometric modelers: a multisector perspective
AbstractThe current demand for pharmacometricians outmatches the supply provided by academic institutions and considerable investments are made to develop the competencies of these scientists on-the-job. Even with the observed increase in academic programs related to pharmacometrics, this need is unlikely to change in the foreseeable future, as the demand and scope of pharmacometrics applications keep expanding. Further, the field of pharmacometrics is changing. The field largely started when Lewis Sheiner and Stuart Beal published their seminal papers on population pharmacokinetics in the late 1970 ’s and early 1980’s...
Source: Journal of Pharmacokinetics and Pharmacodynamics - August 13, 2023 Category: Drugs & Pharmacology Source Type: research

Population pharmacokinetic/pharmacodynamic modeling of nifekalant injection with varies dosing plan in Chinese volunteers: a randomized, blind, placebo-controlled study
In this study, a single-center, randomized, blind, dose-ascending, placebo-controlled study was conducted to explore the intrinsic characteristics of nifekalant injection in healthy Chinese volunteers by a population pharmacokinetic (PK)-pharmacodynamic (PD) model approach. 42 subjects were enrolled in this study and received one of three dose plans (loading dose on Day 1 (0.15, 0.3 or 0.5 mg/kg), loading dose followed by maintenance dose (0.2, 0.4 or 0.8 mg/kg/h) on Day 4) or vehicle. Blood sampl es were drawn for PK evaluation, and ECGs were recorded for QTc calculation at the designed timepoints. No Torsades de Pointe...
Source: Journal of Pharmacokinetics and Pharmacodynamics - August 11, 2023 Category: Drugs & Pharmacology Source Type: research

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