A5022826294- Hemophilia Treatment and Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Platelet Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Antibiotics Pharmacokinetics and Efficacy
- COVID-19 Clinical Research Studies
- Pharmaceutical studies and practices
- SARS-CoV-2 and COVID-19 Research
- Venous Thromboembolism Diagnosis and Management
- SARS-CoV-2 detection and testing
- Colorectal Cancer Treatments and Studies
- Heparin-Induced Thrombocytopenia and Thrombosis
- Pneumonia and Respiratory Infections
- Lung Cancer Treatments and Mutations
- Neonatal and Maternal Infections
- Bacterial Identification and Susceptibility Testing
- HER2/EGFR in Cancer Research
- Hemostasis and retained surgical items
- Protein purification and stability
- Chronic Myeloid Leukemia Treatments
- Analytical Methods in Pharmaceuticals
- Antimicrobial Resistance in Staphylococcus
- Blood disorders and treatments
- Acute Lymphoblastic Leukemia research
- Blood groups and transfusion
Erasmus University Rotterdam
2022-2025
Erasmus MC
2022-2025
Amsterdam University Medical Centers
2019-2024
University of Amsterdam
2019-2024
Amsterdam UMC Location University of Amsterdam
2017-2020
Radboud University Nijmegen
2015
Radboud University Medical Center
2015
Background: Osimertinib is the cornerstone in treatment of epidermal growth factor receptor-mutated non-small cell lung cancer (NSCLC). Nonetheless, ±25% patients experience severe treatment-related toxicities. Currently, it impossible to identify at risk toxicity beforehand. Therefore, we aimed study relationship between osimertinib exposure and a safe toxic limit for preventive dose reduction. Methods: In this real-life prospective cohort study, with NSCLC treated were followed (grade ⩾3...
Abstract Objectives In pediatric patients, vancomycin plays a pivotal role in combating infections, necessitating precise therapeutic drug monitoring to ensure efficacy and safety. The adoption of model-informed precision dosing (MIPD) has demonstrated potential optimizing strategies based on the area under concentration-time curve (AUC24h). However, predictive performance population pharmacokinetic models using only trough concentrations estimate AUC24h not been evaluated. Methods...
Sepsis affects approximately 8% of pediatric intensive care unit (PICU) admissions in high-income countries. Ceftriaxone, a broad-spectrum beta-lactam antibiotic, is widely used for treating severe infections and bacterial meningitis children. Despite its frequent use, limited studies address the population pharmacokinetic (popPK) ceftriaxone pediatrics. External validation popPK models essential to confirm their suitability individualized dosing PICU patients, enabling selection model best...
During the COVID-19 pandemic, trials on convalescent plasma (ConvP) were performed without preceding dose-finding studies. This study aimed to assess potential protective dosing regimens by constructing a population pharmacokinetic (popPK) model describing anti-SARS-CoV-2 antibody titers following administration of ConvP or hyperimmune globulins (COVIg).
Patients with severe and moderate haemophilia A are treated prophylactically factor VIII (FVIII) concentrate. Individualization of prophylaxis can be achieved by pharmacokinetic (PK)-guided dosing.In this study, the performance three PK tools (myPKFiT, Web-Accessible Population Pharmacokinetic Service-Hemophilia [WAPPS] NONMEM) is compared.In 39 patients, or A, blood samples were collected 4, 24 48 hours after administration 50 IU kg-1 recombinant FVIII (Advate [n = 30] Kogenate 9]). dose,...
Abstract Background There is a lack of evidence on oral amoxicillin pharmacokinetics and exposure in neonates with possible serious bacterial infection (pSBI). We aimed to describe disposition following intravenous administration provide dosing recommendations for preterm term treated pSBI. Methods In this pooled-population pharmacokinetic study, 3 datasets were combined nonlinear mixed-effects modeling. order evaluate administration, profiles different regimens simulated the developed...
Data published on the oral clavulanic acid pharmacokinetics in pediatric population is lacking. This research aimed to describe disposition following and intravenous administration provide insights into exposure based threshold concentrations for (pre-)term neonates infants. pooled pharmacokinetic study combined four datasets analysis NONMEM v7.4.3. Clavulanic was simulated using percentage of time above (%fT > C
Essentials Factor IX (FIX) dosing using body weight frequently results in under and overdosing during surgery. We aimed to establish a population pharmacokinetic (PK) model describing the perioperative FIX levels. Population PK parameter values for clearance V1 were 284 mL h-170 kg-1 5450 mL70 kg-1. Perioperative parameters differ from those non-surgical prophylactic treatment. SUMMARY: Background Hemophilia B is bleeding disorder characterized by deficiency of coagulation factor (FIX). In...
In 1985, external quality assurance was initiated in the Netherlands to reduce between-laboratory variability of leukemia/lymphoma immunophenotyping and improve diagnostic conclusions. This program consisted regular distributions test samples followed by biannual plenary participant meetings which results were presented discussed. A scoring system developed rated systematically reviewing pre-analytical, analytical, post-analytical assay stages using three scores, i.e., correct (A), minor...
Haemophilia B is caused by a deficiency of coagulation factor IX (FIX) and characterized bleeding in muscles joints. In the perioperative setting, patients are treated with FIX replacement therapy to secure haemostasis. Targeting specified levels challenging requires frequent monitoring adjustment therapy.To evaluate management haemophilia B, including infusions observed levels, whereby predictors low high were assessed.In this international multicentre study, < 0.05 IU mL-1 undergoing...
Many patients with von Willebrand disease (VWD) are treated on demand factor and VIII (FVIII) containing concentrates present VWF and/or FVIII plasma levels outside set target levels. This carries a risk for bleeding potentially thrombosis. Development of population pharmacokinetic (PK) model based is first step to more accurate on-demand perioperative dosing this concentrate.Patients VWD undergoing surgery in Academic Haemophilia Treatment Centers the Netherlands between 2000 2018 FVIII/VWF...
Under- and, especially, overdosing of replacement therapy in haemophilia A patients may be prevented by application other morphometric variables than body weight (BW) to dose factor VIII (FVIII) concentrates. Therefore, we aimed investigate which best describe interindividual variability (IIV) FVIII concentrate pharmacokinetic (PK) parameters.PK profiling was performed measuring 3 levels after a standardized 50 IU kg-1 concentrate. population PK model constructed, IIV for clearance (CL) and...
Abstract Background The pharmacokinetic (PK) properties of extended half-life (EHL) factor VIII (FVIII) concentrates differ, leading to variation in the optimal dosing regimen for individual patient. aim this study was establish these PK differences various EHL FVIII by silico simulations. Methods level over time profiles rFVIII-SC, BAY 81–8973, rFVIII-Fc, BAX 855, 94–9027, and standard (SHL) rFVIII were simulated 1,000 severe hemophilia A patients during steady-state 40 IU/kg every 72 hours...
Pharmacokinetic (PK) differences between the extended half-life (EHL) factor IX (FIX) concentrates for hemophilia B exist, which may influence hemostatic efficacy of replacement therapy in patients. Therefore, we aimed to evaluate PK properties three EHL-FIX and compare them a standard (SHL) recombinant FIX (rFIX) concentrate.Activity-time profiles PEGylated (N9-GP), linked with human albumin (rIX-FP), coupled IgG1 Fc-domain (rFIXFc), SHL rFIX were simulated 10,000 patients during...
Aims Nadroparin is administered to COVID‐19 intensive care unit (ICU) patients as thromboprophylaxis. Despite existing population pharmacokinetic (PK) models for nadroparin in literature, the PK of ICU unknown. Moreover, optimal dosing regimens achieving anti‐Xa target levels (0.3–0.7 IU/mL) are Therefore, a analysis was conducted investigate different patients. Methods Anti‐Xa ( n = 280) from 65) receiving twice daily (BID) 5700 IU subcutaneous were collected perform with NONMEM v7.4.1....
Individuals with von Willebrand disease (VWD) require desmopressin testing because of interindividual response differences. However, is burdensome, while not all patients may need extensive testing.
Abstract This work focusses on extending the deep compartment model (DCM) framework to estimation of mixed-effects. By introducing random effects, predictions can be personalized based drug measurements, enabling testing different treatment schedules an individual basis. The performance classical first-order (FO and FOCE) machine learning variational inference (VI) algorithms were compared in a simulation study. In VI, posterior distributions variables are approximated using whose parameters...
Abstract Background During the COVID-19 pandemic, trials on convalescent plasma (ConvP) were performed without preceding dose-finding studies. This study aimed to assess potential protective dosing regimens by constructing a population pharmacokinetic (popPK) model describing neutralizing antibody (Nab) titers following administration of ConvP or hyperimmune globulins(COVIg). Methods Immunocompromised patients, testing negative for anti-SARS-CoV-2 spike antibodies despite vaccination...
Population pharmacokinetic (PK) models are increasingly applied to perform individualized dosing of factor VIII (FVIII) concentrates in haemophilia A patients. To guarantee accurate performance a population PK model dose individualization, validation studies importance. However, external requires independent data sets and is, therefore, seldomly performed. Therefore, this study aimed validate previously published for FVIII administrated perioperatively.A concentrate during surgery was...
A 58-year-old morbidly obese male (body mass index: 38 kg/m 2 ) with severe haemophilia underwent total knee replacement surgery. Perioperatively, factor VIII (FVIII) levels were measured daily and maximum a posteriori (MAP) Bayesian estimation was used to calculate the individual pharmacokinetic (PK) parameters doses required obtain prescribed FVIII target levels. In MAP procedure, population PK model in which normalised using body weight. this specific case, ideal weight scale instead of...