Publications by authors named "Daan Touw"

Purpose/background: Clozapine and norclozapine are highly protein bound. Currently, clozapine is increasingly prescribed once daily (QD). Higher (once daily) doses may theoretically lead to saturation of protein binding of (nor)clozapine, resulting in increased unbound fractions.

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Objective: Oral esketamine has relatively low and variable bioavailability, which may complicate broader use as an antidepressant. This study aimed to investigate associations between different pharmacokinetic outcomes and change in depressive symptoms following oral esketamine administration in patients with treatment-resistant depression. Understanding such associations may inform dosing and administration strategies in clinical practice.

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Background: Kidney transplant recipients (KTR) with high-normal lead have a higher risk of graft failure (GF). Clinically, chelation therapy using meso-2,3-dimercaptosuccinic acid (DMSA) removes lead. Despite the proposal that chelation therapy can prevent GF through lead removal, evidence is lacking.

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Aim: Iron is known to play a role in glucose homeostasis, and diabetes is highly prevalent in patients with iron overload. Here, we investigated whether ferritin and hepcidin (as parameters of iron status) are associated with the development of post-transplant diabetes in kidney transplant recipients, a population in which around 10 % is known to have high iron status.

Methods: Prospective data from the TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study from the University Medical Center Groningen, the Netherlands were evaluated, involving stable adult kidney transplant recipients > 1 year after transplantation.

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Monitoring infliximab (IFX) concentrations is crucial for optimizing IFX therapy in children with inflammatory bowel diseases (IBDs) who show low response rates due to inadequate drug exposure. Substantial variation occurs in IFX trough concentrations in paediatric patients. : This study aimed to investigate IFX pharmacokinetics (PK) in children with IBD during both the induction phase and maintenance phases and to identify covariates associated with IFX PK.

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Background: Plasma clearance of iohexol is used to measure glomerular filtration rate, for which a UHPLC-MS/MS analytical method was previously developed. In real-world conditions, samples may be thawed on arrival and sampled in unvalidated matrices, prompting the need for an improved validation. We aim to improve the method for iohexol determination in plasma with enhanced stability testing, optimized calibration curves, and partial validation in additional matrices.

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Objectives: Intravenous midazolam is widely used for sedation in critically ill children. Sometimes, these children develop a paediatric delirium (PD). Our aim was to determine the relationship between midazolam serum concentration and the development of new PD in critically ill children.

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Background: Lamotrigine, an antiseizure medication used for epilepsy and bipolar disorders, is often prescribed to women of childbearing age due to relatively low teratogenic risk. It is known that lamotrigine use in lactation leads to detectable concentrations in breast milk, although concentrations vary significantly among individuals.

Case Presentation: A 35-year-old pregnant woman with epilepsy presented to our outpatient clinic.

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Aligned with the mission of the Dutch Pharmacogenetics Working Group (DPWG) to promote the implementation of pharmacogenetics (PGx), this guideline is specifically designed to optimize pharmacotherapy of cholesterol lowering medication (statins) and glucose lowering medication (sulfonylureas). The SLCO1B1 c.521 T > C variant reduces the activity of the SLCO1B1 transporter involved in statin transport out of the blood into the liver.

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Article Synopsis
  • The aim was to determine whether continuous or multiple daily doses of PTH would be more effective in reducing urinary calcium excretion and lowering the nephrolithiasis risk, using a pharmacokinetic-pharmacodynamic (PKPD) model.
  • The results indicated that continuous PTH infusion significantly improved phosphate clearance, although its effect on calcium clearance was less pronounced, suggesting that further research on continuous administration is warranted.
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  • High-dose methotrexate (HD-MTX) is commonly used to treat patients with central nervous system lymphoma, but it carries risks of unpredictable toxicity and pharmacokinetic variability.
  • The study aimed to characterize the population pharmacokinetics of HD-MTX and identify predictors for the risk of kidney and liver damage.
  • Results indicated that factors like estimated glomerular filtration rate (eGFR), treatment regimen, and MTX dose significantly impact PK variability and toxicity risk, with specific concentration thresholds linked to increased chances of nephrotoxicity.
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Background: This report presents the case of a patient with drug-resistant epilepsy. Despite treatment with 4 antiepileptic drugs, the patient experienced an increasing frequency of focal seizures, necessitating hospitalization, and continuous intravenous midazolam infusion.

Methods: Cobicistat was introduced as a pharmacokinetic booster to decrease the metabolic clearance of midazolam, leading to increased exposure and an extended half-life.

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Background: Valacyclovir-induced neurotoxicity is a rare side effect. The aim of this study was to perform a retrospective analysis of patients with valacyclovir-induced neurotoxicity and establish valacyclovir plasma concentrations in a tertiary hospital between January 2018 and November 2022.

Case Descriptions: In total 208 patients were identified with measured acyclovir concentrations, and the electronic health records of these patients were analysed.

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Article Synopsis
  • Infliximab is used to treat inflammatory bowel disease (IBD) and its trough concentrations (C-troughs) are important for optimizing treatment efficacy, traditionally measured using ELISA tests.
  • A study compared the new Quantum Blue® lateral flow test with traditional ELISA for measuring C-troughs in 100 young IBD patients and found that both methods had good agreement, particularly in low-range measurements.
  • The results indicated that lateral flow tests are a reliable, quicker alternative to ELISA, allowing for timely dose adjustments in patients experiencing active disease.
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Aims: Digoxin is the oldest drug in cardiovascular (CV) medicine, and one trial conducted >25 years ago showed a reduction in heart failure (HF) hospitalizations but no effect on mortality. However, later studies suggested that the dose of digoxin used in that trial (and other studies) may have been too high. The DECISION (Digoxin Evaluation in Chronic heart failure: Investigational Study In Outpatients in the Netherlands) trial will examine the efficacy and safety of low-dose digoxin in HF patients with reduced or mildly reduced left ventricular ejection fraction (LVEF) with a background of contemporary HF treatment.

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Clozapine remains the only pharmacological treatment option for treatment-resistant schizophrenia. Therapeutic drug monitoring (TDM) of clozapine is recommended, although evidence for the therapeutic range of 350-600 ng/ml is limited. In various countries including Serbia, TDM of clozapine is not routinely performed.

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Introduction And Objective: Pazopanib is registered for metastatic renal cell carcinoma and soft-tissue sarcoma (STS). Its variable pharmacokinetic (PK) characteristics and narrow therapeutic range provide a strong rationale for therapeutic drug monitoring (TDM). Prior studies have defined target levels of drug exposure (≥ 20.

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Metformin is the most widely used drug in type 2 diabetes. Regular metformin use has been associated with changes in concentrations of amino acids. In the present study, we used valid stable-isotope labeled GC-MS methods to measure amino acids and metabolites, including creatinine as well as malondialdehyde (MDA), as an oxidative stress biomarker in plasma, urine, and dialysate samples in a patient at admission to the intensive care unit and during renal replacement treatment because of metformin-associated lactic acidosis (MALA, 21 mM lactate, 175 µM metformin).

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Background: Therapeutic drug monitoring (TDM) - performing dose adjustments based on measured drug levels and established pharmacokinetic (PK) targets - could optimise treatment with drugs that show large interpatient variability in exposure. We evaluated the feasibility of TDM for multiple oral targeted therapies. Here we report on drugs for which routine TDM is not feasible.

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The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate pharmacogenetics implementation in clinical practice by developing evidence-based guidelines to optimize pharmacotherapy based on pharmacogenetic test results. The current guideline describes the gene-drug interaction between CYP2D6 and venlafaxine, mirtazapine and duloxetine. In addition, the interaction between CYP2C19 and mirtazapine and moclobemide is presented.

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This study employed physiologically-based pharmacokinetic-pharmacodynamics (PBPK/PD) modeling to predict the effect of obesity and gastric bypass surgery on the pharmacokinetics and intragastric pH following omeprazole treatment. The simulated plasma concentrations closely matched the observed data from non-obese, morbidly obese, and post-gastric bypass populations. Obesity significantly reduces CYP3A4 and CYP2C19 activities, as reflected by the metabolic ratio [omeprazole sulphone]/[omeprazole] and [5-hydroxy-omeprazole]/[omeprazole].

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Background And Objective: Several population pharmacokinetic (popPK) studies have been reported that can guide the prediction of osimertinib plasma concentrations in individual patients. It is currently unclear which popPK model offers the best predictive performance and which popPK models are most suitable for nonadherence management and model-informed precision dosing. Therefore, the objective of this study was to externally validate all osimertinib popPK models available in the current literature.

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Aims: Use of infliximab (IFX) has improved outcomes in children with inflammatory bowel disease (IBD). However, a proportion of patients does not respond to IFX or loses response over time. Population pharmacokinetic (PopPK) modelling is a promising approach for IFX dose optimization, but with the increasing number of PopPK models in literature, model evaluation is essential.

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