A5002881595- Pharmacogenetics and Drug Metabolism
- Antibiotics Pharmacokinetics and Efficacy
- Statistical Methods in Clinical Trials
- Pharmaceutical studies and practices
- Drug Transport and Resistance Mechanisms
- Pediatric Pain Management Techniques
- Drug-Induced Hepatotoxicity and Protection
- Blood Pressure and Hypertension Studies
- Hemodynamic Monitoring and Therapy
- Metabolomics and Mass Spectrometry Studies
- Drug-Induced Adverse Reactions
- Pharmacological Effects and Toxicity Studies
- Liver Disease Diagnosis and Treatment
- Liver Disease and Transplantation
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Poisoning and overdose treatments
- Anesthesia and Sedative Agents
- Pancreatic function and diabetes
- Statistical Methods and Bayesian Inference
- Advanced Causal Inference Techniques
- Congenital Ear and Nasal Anomalies
- Hormonal Regulation and Hypertension
- Metabolism and Genetic Disorders
- Analytical Chemistry and Chromatography
- Analytical Methods in Pharmaceuticals
Sanofi (France)
2020-2025
Centre for Human Drug Research
2016-2019
Leiden University
2016-2019
Allometric scaling on the basis of bodyweight raised to power 0.75 (AS0.75) is frequently used scale size-related changes in plasma clearance (CLp) from adults children. A systematic assessment its applicability undertaken for scenarios considering with and without maturation processes. physiologically-based pharmacokinetic (PBPK) simulation workflow was developed R 12,620 hypothetical drugs. In scenario one, only liver weight, hepatic blood flow, glomerular filtration were included...
Objective: To compare the pharmacodynamics and pharmacokinetics of IV morphine after cardiac surgery in two groups children—those with without Down syndrome. Design: Prospective, single-center observational trial. Setting: PICU a university-affiliated pediatric teaching hospital. Patients: Twenty-one children syndrome 17 without, 3–36 months old, scheduled for cardiopulmonary bypass. Interventions: A loading dose (100 μg/kg) was administered coming off bypass; thereafter, infusion commenced...
For scaling drug plasma clearance (CLp) from adults to children, extrapolations of population pharmacokinetic (PopPK) covariate models between drugs sharing an elimination pathway have enabled accelerated development pediatric and dosing recommendations. This study aims at identifying conditions for which this approach consistently leads accurate specific CLp children undergoing hepatic metabolism. A physiologically based (PBPK) simulation workflow utilizing mechanistic equations defining...
Previous research showed that scaling drug clearance from adults to children based on body weight alone is not accurate for all hepatically cleared drugs in very young children. This study systematically assesses the accuracy of methods that, addition weight, also take age-based variables into account undergoing hepatic metabolism younger than five years, namely with (1) a weight-based function using an age-dependent exponent (ADE) and (2) fixed 0.75 (AS0.75) combined isoenzyme maturation...
Although children cannot be considered small adults due to nonlinear processes underlying the pharmacokinetics of drugs, pediatric doses are typically still expressed per kilogram. We use a physiologically based pharmacokinetic (PBPK) workflow assess accuracy linear scaling plasma clearance ( CL p) for hypothetical drugs with ranges realistic parameter values in patients different ages. The results compared 0.75 fixed allometric (AS 0.75). Linear p is accurate down age 1 month undergoing...
Decreasing morbidity and mortality by rationalizing drug treatment in the critically ill is of paramount importance but challenging as underlying clinical condition may lead to large variation disposition response. New microtracer methodology now available gain knowledge on intensive care. On basis studies healthy adults, physicians tend assume that oral doses acetaminophen will be completely absorbed therefore prescribe same dose per kilogram for IV administration. As bioavailability...
In covariate (sub)models of population pharmacokinetic models, most covariates are normalized to the median value; however, for body weight, normalization 70 kg or 1 is often applied. this article, we illustrate impact weight on precision clearance (CLpop) parameter estimates. The influence (70, weight) CLpop estimate, expressed as relative standard error (RSE), was illustrated using data from a study in neonates with 2.7 kg. addition, simulation performed show studies paediatric obese...
Physiologically-based pharmacokinetic (PBPK) models are essential in drug development, but require parameters that not always obtainable. We developed a methodology to investigate the feasibility and requirements for precise accurate estimation of PBPK using population modelling clinical data illustrate this two key hepatic metabolic clearance, namely whole liver unbound intrinsic clearance (CLint,u,WL) blood flow (Qh) children.First, structural identifiability was enabled through...
Recently a framework was presented to assess whether pediatric covariate models for clearance can be extrapolated between drugs sharing elimination pathways, based on extraction ratio, protein binding, and other drug properties. Here we evaluate when function midazolam used scale of CYP3A substrates. A population PK model including developed in children aged 1–17 years. Commonly substrates were selected using the framework, it assessed accurately scales their clearance. For eight substrates,...
Drug clearance in obese subjects varies widely among different drugs and across with severity of obesity. This study investigates correlations between plasma (CLp) drug- patient-related characteristics subjects, evaluates the systematic accuracy common weight-based dosing methods. A physiologically-based pharmacokinetic (PBPK) modeling approach that uses recent information on obesity-related changes physiology was used to simulate CLp for a normal-weight subject (body mass index [BMI] = 20)...
Background Despite being the most commonly used analgesic and antipyretic, oral APAP bioavailability has not been determined in children. The aim of this study is to compare exposure after vs iv using PK data first pediatric 14C microtracer study. Methods Design population Participants patients < 6 yrs old ICU who received 15 mg/kg q6h Intervention a single microdose (3µg/kg) given orally at same time as therapeutic dose Data collection Blood was sampled 8 times up 24 h post-dose analysis...