4 results match your criteria: "The Netherlands. e.krekels@lacdr.leidenuniv.nl.[Affiliation]"
Changes in Plasma Clearance of CYP450 Probe Drugs May Not be Specific for Altered In Vivo Enzyme Activity Under (Patho)Physiological Conditions: How to Interpret Findings of Probe Cocktail Studies.
Clin Pharmacokinet
November 2024
Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Article Synopsis
- CYP450 phenotyping measures how well an individual's body processes specific probe drugs to infer activity of CYP enzymes, important for understanding drug metabolism in varying health conditions like obesity or pregnancy.
- The study used a physiologically based pharmacokinetic approach to determine if plasma clearance of these drugs truly reflects CYP enzyme activity and how much factors like protein binding or blood flow affect this clearance.
- Results show that while plasma clearance generally responds to changes in CYP activity, it is also significantly influenced by the unbound drug fraction, particularly for drugs that are high in protein binding, limiting the accuracy of using plasma clearance as a sole measure of CYP activity.
Larger Dose Reductions of Vancomycin Required in Neonates with Patent Ductus Arteriosus Receiving Indomethacin versus Ibuprofen.
Antimicrob Agents Chemother
August 2019
Division of Biomedicine and Systems Pharmacology, Leiden University, Leiden, The Netherlands
Ibuprofen and indomethacin are commonly used to induce ductus arteriosus closure in preterm neonates. Our group previously reported that ibuprofen decreased vancomycin clearance by 16%. In this study, we quantified the impact of indomethacin coadministration on vancomycin clearance by extending our vancomycin population pharmacokinetic model with a data set containing vancomycin concentrations measured in preterm neonates comedicated with indomethacin.
View Article and Find Full Text PDFKernel-Based Visual Hazard Comparison (kbVHC): a Simulation-Free Diagnostic for Parametric Repeated Time-to-Event Models.
AAPS J
November 2017
Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333, CC, Leiden, The Netherlands.
Repeated time-to-event (RTTE) models are the preferred method to characterize the repeated occurrence of clinical events. Commonly used diagnostics for parametric RTTE models require representative simulations, which may be difficult to generate in situations with dose titration or informative dropout. Here, we present a novel simulation-free diagnostic tool for parametric RTTE models; the kernel-based visual hazard comparison (kbVHC).
View Article and Find Full Text PDFPopulation Pharmacokinetics of Edoxaban in Patients with Non-Valvular Atrial Fibrillation in the ENGAGE AF-TIMI 48 Study, a Phase III Clinical Trial.
Clin Pharmacokinet
September 2016
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Introduction: Edoxaban is a novel factor Xa inhibitor. This study characterizes the population pharmacokinetics of edoxaban in patients with non-valvular atrial fibrillation (NVAF) included in the phase III ENGAGE AF-TIMI 48 study, evaluates covariates for the dose-exposure relationship in this population, and assesses the impact of protocol-specified dose reductions on exposure using simulations.
Methods: Model development was performed using NONMEM(®) and based on sparse data from the ENGAGE AF-TIMI 48 study augmented with dense data from 13 phase I studies to inform and stabilize the model.