-
Article
Open AccessMixed effect estimation in deep compartment models: Variational methods outperform first-order approximations
This work focusses on extending the deep compartment model (DCM) framework to the estimation of mixed-effects. By introducing random effects, model predictions can be personalized based on drug measurements, e...
-
Article
Open AccessPopulation Pharmacokinetics of Adalimumab in Juvenile Idiopathic Arthritis Patients: A Retrospective Cohort Study Using Clinical Care Data
Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disorder that primarily affects the joints in children. Notably, it is known to co-occur with uveitis. Adalimumab, a monoclonal anti-TNF antibody, is...
-
Article
Open AccessOn inductive biases for the robust and interpretable prediction of drug concentrations using deep compartment models
Conventional pharmacokinetic (PK) models contain several useful inductive biases guiding model convergence to more realistic predictions of drug concentrations. Implementing similar biases in standard neural n...
-
Article
Open AccessPharmacokinetic–Pharmacodynamic Modelling in Hemophilia A: Relating Thrombin and Plasmin Generation to Factor VIII Activity After Administration of a VWF/FVIII Concentrate
Hemophilia A patients are treated with factor (F) VIII prophylactically to prevent bleeding. In general, dosage and frequency are based on pharmacokinetic measurements. Ideally, an alternative dose adjustment ...
-
Article
Open AccessBenzylpenicillin concentrations in umbilical cord blood and plasma of premature neonates following intrapartum doses for group B streptococcal prophylaxis
Dutch obstetrics guideline suggest an initial maternal benzylpenicillin dose of 2,000,000 IU followed by 1,000,000 IU every 4 h for group-B-streptococci (GBS) prophylaxis. The objective of this study was to ev...
-
Article
Open AccessRight dose, right now: bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock—a two-centre randomised clinical trial
Adequate antibiotic dosing may improve outcomes in critically ill patients but is challenging due to altered and variable pharmacokinetics. To address this challenge, AutoKinetics was developed, a decision sup...
-
Article
Open AccessClinical Pharmacokinetics of Gentamicin in Various Patient Populations and Consequences for Optimal Dosing for Gram-Negative Infections: An Updated Review
Gentamicin is an aminoglycoside antibiotic with a small therapeutic window that is currently used primarily as part of short-term empirical combination therapy. Gentamicin dosing schemes still need refinement,...
-
Article
Open AccessCurrent Ceftriaxone Dose Recommendations are Adequate for Most Critically Ill Children: Results of a Population Pharmacokinetic Modeling and Simulation Study
Ceftriaxone is a cornerstone antibiotic for critically ill children with severe infections. Despite its widespread use, information on the pharmacokinetics of ceftriaxone is lacking in this population. We aime...
-
Article
Open AccessTranscapillary escape rate of 125I-albumin in relation to timing of blood sampling: the need for standardization
Increased vascular permeability is an early sign of vascular damage and can be measured with the transcapillary escape rate of albumin (TERalb). Although TERalb has a multi-exponential kinetic model, most publish...
-
Article
Open AccessWound infection following implant removal of foot, ankle, lower leg or patella; a protocol for a multicenter randomized controlled trial investigating the (cost-)effectiveness of 2 g of prophylactic cefazolin compared to placebo (WIFI-2 trial)
Elective implant removal (IR) after fracture fixation is one of the most common procedures within (orthopedic) trauma surgery. The rate of surgical site infections (SSIs) in this procedure is quite high, espec...
-
Article
Open AccessPopulation Pharmacokinetics of Clotting Factor Concentrates and Desmopressin in Hemophilia
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−1) and some patients with moderate hemophilia (0.01–0.0...
-
Article
Open AccessCorrection to: Optimizing Predictive Performance of Bayesian Forecasting for Vancomycin Concentration in Intensive Care Patients
This article was updated to correct Figs. 1 and 4 as author corrections were overlooked during the production process.
-
Article
Open AccessOptimizing Predictive Performance of Bayesian Forecasting for Vancomycin Concentration in Intensive Care Patients
Bayesian forecasting is crucial for model-based dose optimization based on therapeutic drug monitoring (TDM) data of vancomycin in intensive care (ICU) patients. We aimed to evaluate the performance of Bayesia...
-
Article
Open AccessEfficacy and safety of FOLFIRINOX as salvage treatment in advanced biliary tract cancer: an open-label, single arm, phase 2 trial
No standard treatment is available for advanced biliary tract cancer (BTC) after first-line therapy with gemcitabine plus cisplatin (GEMCIS). The objective of this study was to evaluate safety and anti-tumour ...
-
Article
Open AccessTumor necrosis factor-mediated disposition of infliximab in ulcerative colitis patients
Ulcerative Colitis (UC) is an inflammatory bowel disease typically affecting the colon. Patients with active UC have elevated tumor necrosis factor (TNF) concentrations in serum and colonic tissue. Infliximab ...
-
Article
Open AccessClinical Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Ulcerative Colitis
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) of unknown etiology, probably caused by a combination of genetic and environmental factors. The treatment of patients with active UC depends on th...
-
Article
Open AccessNutritional Status Differentially Alters Cytochrome P450 3A4 (CYP3A4) and Uridine 5′-Diphospho-Glucuronosyltransferase (UGT) Mediated Drug Metabolism: Effect of Short-Term Fasting and High Fat Diet on Midazolam Metabolism
Previous studies have shown that nutritional status can alter drug metabolism which may result in treatment failure or untoward side effects. This study assesses the effect of two nutritional conditions, short...
-
Article
Open AccessShort-Term Fasting Alters Pharmacokinetics of Cytochrome P450 Probe Drugs: Does Protein Binding Play a Role?
Short-term fasting differentially alters cytochrome P450 (CYP) mediated drug metabolism. This has been established by using CYP-enzyme selective probe drugs. However, the observed effects of fasting on the pha...
-
Article
Open AccessParacetamol clinical dosing routine leads to paracetamol underexposure in an adult severely ill sub-Saharan African hospital population: a drug concentration measurement study
Hospitals in sub-Saharan Africa (SSA) continue to receive high numbers of severely ill (HIV-infected) patients with physical pain that may suffer from hepatic and renal dysfunction. Paracetamol is widely used ...
-
Article
Open AccessEffect of Short-Term Fasting on Systemic Cytochrome P450-Mediated Drug Metabolism in Healthy Subjects: A Randomized, Controlled, Crossover Study Using a Cocktail Approach
Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance. Therefore, the aim of our study was to assess the effect of sho...
