Publications by authors named "Tim Preijers"

Article Synopsis
  • - Achieving successful antimicrobial therapy requires personalized drug dosing due to differences in how patients metabolize drugs and their pathogens' susceptibility, which is reflected in minimum inhibitory concentration (MIC) values.
  • - Therapeutic drug monitoring (TDM) and population pharmacokinetic (popPK) models help tailor dosing regimens by analyzing drug behavior across various patients, while machine learning (ML) techniques can enhance dose individualization by identifying patterns in large datasets.
  • - The challenge is to balance model complexity with practical clinical application, ensuring regulatory compliance, accurate outcome measurement, and the incorporation of new technologies like real-time biosensors for better monitoring and adjustments in treatment.
View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the pharmacokinetics of oral clavulanic acid in neonates and infants, as existing data on this topic is limited.
  • It analyzes combined data from four datasets using a one-compartment model to determine dosing regimens and exposure levels based on age and body weight.
  • Findings indicate that an amoxicillin/clavulanic acid ratio of 4:1 is optimal, with significant differences in exposure levels based on varying threshold concentrations, laying groundwork for future research.
View Article and Find Full Text PDF

Background And Objective: 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 the administration of ConvP or hyperimmune globulins (COVIg).

Methods: Immunocompromised patients, testing negative for anti-SARS-CoV-2 spike antibodies despite vaccination, received a range of anti-SARS-CoV-2 antibodies in the form of COVIg or ConvP infusion.

View Article and Find Full Text PDF

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 amoxicillin disposition following oral and intravenous administration and to provide dosing recommendations for preterm and term neonates treated for pSBI.

Methods: In this pooled-population pharmacokinetic study, 3 datasets were combined for nonlinear mixed-effects modeling.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the population pharmacokinetics (PK) of nadroparin in COVID-19 ICU patients to determine optimal dosing for effective thromboprophylaxis, as existing models do not specifically address this group.
  • Data was collected from 65 patients receiving 5700 IU of nadroparin twice daily, and analysis revealed that factors like inflammation markers, corticosteroid use, and kidney function significantly influenced drug clearance.
  • The findings suggest that the 5700 IU BID dosing regimen is most effective for achieving target anti-Xa levels, with further research needed to understand the interactions between inflammation and drug clearance better.
View Article and Find Full Text PDF

Background: Osimertinib is the cornerstone in the treatment of epidermal growth factor receptor-mutated non-small cell lung cancer (NSCLC). Nonetheless, ±25% of patients experience severe treatment-related toxicities. Currently, it is impossible to identify patients at risk of severe toxicity beforehand.

View Article and Find Full Text PDF

Background: Dosing of replacement therapy with factor VIII concentrate in patients with haemophilia A in the perioperative setting is challenging. Underdosing and overdosing of factor VIII concentrate should be avoided to minimise risk of perioperative bleeding and treatment costs. We hypothesised that dosing of factor VIII concentrate on the basis of a patient's pharmacokinetic profile instead of bodyweight, which is standard treatment, would reduce factor VIII consumption and improve the accuracy of attained factor VIII levels.

View Article and Find Full Text PDF

Aims: Population pharmacokinetic (PK) models are increasingly applied to perform individualized dosing of factor VIII (FVIII) concentrates in haemophilia A patients. To guarantee accurate performance of a population PK model in dose individualization, validation studies are of importance. However, external validation of population PK models requires independent data sets and is, therefore, seldomly performed.

View Article and Find Full Text PDF

Purpose: 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 the PK properties of three EHL-FIX concentrates and compare them to a standard half-life (SHL) recombinant FIX (rFIX) concentrate.

Methods: Activity-time profiles of PEGylated FIX (N9-GP), FIX linked with human albumin (rIX-FP), FIX coupled to human IgG1 Fc-domain (rFIXFc), and SHL rFIX were simulated for 10,000 patients during steady-state dosing of 40 IU/kg once weekly (EHL-FIX) and biweekly (rFIX) using published concentrate specific population PK models.

View Article and Find Full Text PDF

Background:  The pharmacokinetic (PK) properties of extended half-life (EHL) factor VIII (FVIII) concentrates differ, leading to variation in the optimal dosing regimen for the individual patient. The aim of this study was to establish these PK differences for various EHL FVIII concentrates by in silico simulations.

Methods:  FVIII level over time profiles of rFVIII-SC, BAY 81-8973, rFVIII-Fc, BAX 855, BAY 94-9027, and standard half-life (SHL) rFVIII concentrates were simulated for 1,000 severe hemophilia A patients during steady-state dosing of 40 IU/kg every 72 hours or dosing as advised in the summary of product characteristics (SmPC).

View Article and Find Full Text PDF

Aims: Under- and, especially, overdosing of replacement therapy in haemophilia A patients may be prevented by application of other morphometric variables than body weight (BW) to dose factor VIII (FVIII) concentrates. Therefore, we aimed to investigate which morphometric variables best describe interindividual variability (IIV) of FVIII concentrate pharmacokinetic (PK) parameters.

Methods: PK profiling was performed by measuring 3 FVIII levels after a standardized dose of 50 IU kg FVIII concentrate.

View Article and Find Full Text PDF

Hemophilia A and B are bleeding disorders caused by a deficiency of clotting factor VIII and IX, respectively. Patients with severe hemophilia (< 0.01 IU mL) and some patients with moderate hemophilia (0.

View Article and Find Full Text PDF

Hemophilia A and hemophilia B are hereditary bleeding disorders, caused by a deficiency of clotting factor VIII or clotting factor IX, respectively. To treat and prevent bleedings, patients can administer clotting factor concentrates (hemophilia A and B) or desmopressin (hemophilia A). Both clotting factor concentrates and desmopressin are currently dosed according to the patients' body weight.

View Article and Find Full Text PDF

A 58-year-old morbidly obese male (body mass index: 38 kg/m) with severe haemophilia A underwent total knee replacement surgery. Perioperatively, factor VIII (FVIII) levels were measured daily and maximum (MAP) Bayesian estimation was used to calculate the individual pharmacokinetic (PK) parameters and doses required to obtain prescribed FVIII target levels. In the MAP Bayesian procedure, a population PK model was used in which PK parameters were normalised using body weight.

View Article and Find Full Text PDF

In 1985, external quality assurance was initiated in the Netherlands to reduce the between-laboratory variability of leukemia/lymphoma immunophenotyping and to improve diagnostic conclusions. This program consisted of regular distributions of test samples followed by biannual plenary participant meetings in which results were presented and discussed. A scoring system was developed in which the quality of results was rated by systematically reviewing the pre-analytical, analytical, and post-analytical assay stages using three scores, i.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session6v8op8e0bb95j8b5q6q0i3sbbvq8j5g3): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once