Erik Van Maarseveen

University Medical Center Utrecht | UMC Utrecht · Department of Pharmacy

Objective: To assess the relationship of adalimumab trough concentrations and treatment response in paediatric patients with juvenile idiopathic arthritis (JIA). Methods: Monocentric cohort study of JIA patients treated with adalimumab. Clinical data and samples were collected during routine follow-up. Adalimumab trough concentrations were quant...

Background Non-adherence to antihypertensive drugs is an important behavioral contributor to poor blood pressure control and is associated with increased risk of cardiovascular disease, hospitalization and increased healthcare costs. Biochemical drug screening in plasma is an accurate method for the detection of non-adherence. When performed qualit...

Introduction Haemophilia A is a hereditary bleeding disorder caused by a factor VIII (FVIII) deficiency. As biomarker, FVIII activity is used to classify disease severity and to monitor treatment. The one‐stage clotting assay (OSA) is performed to measure FVIII activity, but OSA's limitations may result in misclassification of disease severity or s...

The addition of rabbit anti-human thymocyte globulin (ATG) to the conditioning regimen prior to allogeneic hematopoietic cell transplantation has significantly reduced the risk of graft-versus-host disease (GvHD) and graft failure. However, ATG has a small therapeutic window. Overexposure of ATG post-HCT hampers T cell immune reconstitution and has...

Background: Studies comparing the clinical outcomes between vancomycin intermittent infusion (InI) and continuous infusion (CoI) treated patients are generally underpowered. Moreover, due to large differences in the design and efficacy end points in these studies, a meta-analysis of the currently available data is not feasible. Therefore, this sys...

Aim To develop a semi‐mechanistic model, based on glutathione depletion and predict a previously identified intra‐individual reduction in busulfan clearance to aid in more precise dosing. Methods Busulfan concentration data, measured as part of regular care for allogeneic hematopoietic cell transplantation (HCT) patients, were used to develop a se...

Background: In the era of multiple daily dosing of systemic aminoglycosides, a circadian rhythm in the clearance of these vital antibiotics has been demonstrated in animals and healthy volunteers. Over the past decade, once-daily dosing regimens have been proved to be less nephrotoxic and were therefore adopted worldwide for most indications requi...

Optimal fludarabine exposure has been associated with improved treatment outcome in allogeneic hematopoietic cell transplantation (HCT), suggesting potential benefit of individualized dosing. A randomized controlled trial (RCT) comparing alternative fludarabine dosing strategies to current practice may be warranted, but should be sufficiently power...

The calcineurin inhibitor tacrolimus is an effective immunosuppressant and is extensively used in solid organ transplantation. In the first week after heart and lung transplantation, tacrolimus dosing is difficult due to considerable physiological changes because of clinical instability, and toxicity often occurs, even when tacrolimus concentration...

Background and objective: Therapeutic drug monitoring of tacrolimus whole-blood concentrations is standard care in thoracic organ transplantation. Nevertheless, toxicity may appear with alleged therapeutic concentrations possibly related to variability in unbound concentrations. However, pharmacokinetic data on unbound concentrations are not avail...

Background: The aim of this study was to improve the predictive power of patient-derived xenografts (PDXs, also known as mouse avatars) to more accurately reflect outcomes of clofarabine-based treatment in pediatric acute lymphoblastic leukemia (ALL) patients. Procedure: Pharmacokinetic (PK) studies were conducted using clofarabine at 3.5 to 15...

Background and Objective Oral tacrolimus is initiated perioperatively in heart and lung transplantation patients. There have been few studies on oral tacrolimus pharmacokinetics early post-transplantation, even though tacrolimus-related toxicity may occur early, potentially leading to morbidity and mortality. Therefore, we aimed to study the pharma...

Background Busulfan is widely used as conditioning in allogeneic haematopoietic cell transplantation (allo-HCT) and has a narrow therapeutic range (80-100 mg*hr/L). Primary objective was to examine the effect of therapeutic drug monitoring (TDM) on attaining busulfan target exposure in children and adults undergoing allo-HCT. Secondarily, we studie...

Background/Introduction Antihypertensive medication screening by qualitative high performance chromatography-tandem mass spectrometry (LC-MS/MS) has recently become available to detect non-adherence to antihypertensive treatment. Because the result of this test is dichotomous (the drug is detected or not), it may incorrectly classify patients who t...

Background and Purpose Corticosteroids are intra‐articularly injected to relieve pain in joints with osteoarthritis (OA) or acute tissue damage such as ligament or tendon tears, despite its unverified contraindication in unstable joints. Biomaterial‐based sustained delivery may prolong reduction of inflammatory pain, while avoiding harmful peak dru...

Fludarabine is the most frequently used agent in conditioning regimens for allogeneic hematopoietic cell transplantation (HCT). Body surface area-based dosing leads to highly variable fludarabine exposure. We studied the relation between fludarabine exposure and clinical outcomes. A retrospective, pharmacokinetic-pharmacodynamic analysis was conduc...

Aims To individualize treatment, phenytoin doses are adjusted based on free concentrations, either measured or calculated from total concentrations. As a mechanistic protein binding model may more accurately reflect the protein binding of phenytoin than the empirical Winter–Tozer equation that is routinely used for calculation of free concentration...

Background The development of anti-drug antibodies (ADA) in patients treated with therapeutic proteins can result in treatment failure. The clinically most relevant fraction of these antibodies are the neutralizing anti-drug antibodies (NAb) that block the pharmacological function of the drug. Consequently, the detection of NAb in plasma is a bette...

The promising pipeline of therapeutic monoclonal antibodies (mAbs) demands robust bioanalytical methods with swift development times for pharmacokinetic studies. Over the past decades ligand binding assays were the methods of choice for absolute quantification. However, the production of the required anti-idiotypic antibodies and ligands limits hig...

Background During inflammation, elevated total (unbound plus protein-bound) clozapine plasma concentrations have been observed. Elevated alpha-1-acid glycoprotein concentrations during inflammation are suggested to cause increased plasma clozapine-alpha-1-acid glycoprotein binding, resulting in elevated total clozapine plasma concentrations without...

Adherence to cardiovascular preventive agents is important to prevent short and long term cardiovascular events. Recently, qualitatively compound screening using liquid chromatography-tandem mass spectrometry (LC-MS/MS) has gained interest for drug adherence assessment in patients at high risk of cardiovascular events. Therefore, we developed and t...

Aims We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I‐neb device to the standard PARI‐LC Plus nebulizer in children with cystic fibrosis. Methods A randomized, open‐label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected foll...

Background: Therapeutic drug monitoring of tumor necrosis factor alpha (TNF-α) inhibitors such as adalimumab (ADM) and infliximab (IFX) is considered of added value for patients with systemic inflammatory diseases. In contrast to enzyme-linked immunosorbent assay methods, liquid chromatography-tandem mass spectrometry methods allow for simultaneou...

Objective: The clinical impact of anti-drug antibodies (ADAbs) in paediatric patients with JIA remains unknown. This systematic review and meta-analysis aimed to summarize the prevalence of ADAbs in JIA studies; investigate the effect of ADAbs on treatment efficacy and adverse events; and explore the effect of immunosuppressive therapy on antibody...

Background Fludarabine is often used as an important drug in reduced toxicity conditioning regimens prior to hematopoietic cell transplantation (HCT). As no definitive pharmacokinetic (PK) basis for HCT dosing for the wide age and weight range in HCT is available, linear body surface area (BSA)-based dosing is still used. Objective We sought to de...

Neuroblastoma is one of the most commonly found solid tumors in children. The monoclonal antibody dinutuximab (DNX) targets the sialic acid-containing glycosphingolipid GD2 expressed on almost all neuroblastoma tumor cells and induces cell lysis. However, the expression of GD2 is not limited to tumor cells only, but is also present on central nerve...

Dried blood spot (DBS) sampling is a patient-friendly alternative for plasma sampling for the purpose of therapeutic drug monitoring (TDM). To speed up the analysis time, an automated flow-through desorption method of DBS samples may be beneficial. This article describes the cross-validation of a manual punch DBS method with an automated desorption...

Favipiravir is a novel antiviral drug approved for influenza treatment in Japan. Little is known about favipiravir pharmacokinetics in critically ill patients. Here, we report a patient with influenza treated with favipiravir and undergoing continuous venovenous hemofiltration (CVVH) on the Intensive Care Unit of a tertiary hospital in the Netherla...

The effect of lowering sympathetic nerve activity by renal denervation (RDN) is highly variable. With the exception of office systolic blood pressure (BP), predictors of the BP-lowering effect have not been identified. Because dietary sodium intake influences sympathetic drive, and, conversely, sympathetic activity influences salt sensitivity in hy...

Introduction: Hypertension is only controlled in approximately 35% of the patients, which could be partially due to non-adherence. Recently, bioanalytical assessment of adherence to blood pressure (BP) lowering drugs has gaining interest. Our aim was to explore possible determinants of non-adherence in treatment resistant hypertension, assessed by...

Background: Tacrolimus and mycophenolic acid (MPA) are the backbone of immunosuppressive therapy after pediatric kidney transplantation. Dosing of these drugs is individualized by therapeutic drug monitoring. Dried blood spot (DBS) sampling may prove beneficial over conventional venous sampling. We aimed to develop and clinically validate a DBS me...

A variety of conditional knock-out mice relying on Tamoxifen-driven ERT2/Cre -mediated recombination are available and have been used to study involvement of specific genes in kidney disease. However, recent data suggest that Tamoxifen itself might attenuate fibrosis when administered during experimental models of kidney disease. It has remained un...

A variety of conditional knock-out mice relying on Tamoxifen-driven ERT2/Cre -mediated recombination are available and have been used to study involvement of specific genes in kidney disease. However, recent data suggest that Tamoxifen itself might attenuate fibrosis when administered during experimental models of kidney disease. It has remained un...

In allogeneic hematopoietic cell transplantation (HCT) it has been shown that over- or underexposure to conditioning agents have an impact on patient outcomes. Conditioning regimens combining busulfan (Bu) and fludarabine (Flu) with or without clofarabine (Clo) are gaining interest worldwide in HCT. To evaluate and possibly adjust full conditioning...

Randomized trials of catheter-based renal denervation (RDN) as therapy for resistant hypertension showed conflicting results in blood pressure (BP) lowering effect. Adherence to medication is modest in this patient group and may importantly drive these conflicting results. SYMPATHY is a prospective open label multicenter trial in Dutch patients wit...

Controlled biomaterial-based corticosteroid release might circumvent multiple injections and the accompanying risks, such as hormone imbalance and muscle weakness, in osteoarthritic (OA) patients. For this purpose, microspheres were prepared from an amino acid-based polyester amide (PEA) platform and loaded with triamcinolone acetonide (TAA). TAA l...

Abuse of new psychoactive substances (NPS) and the number of patients presenting to the ER with intoxication are increasing. Treatment may at first sight seem complicated because of limited knowledge of the substance involved, but should be based on a general supportive approach recognising the relatively predictable spectrum of symptoms caused by...

Abuse of new psychoactive substances (NPS) and the number of patients presenting to the ER with intoxication are increasing. Treatment may at first sight seem complicated because of limited knowledge of the substance involved, but should be based on a general supportive approach recognising the relatively predictable spectrum of symptoms caused by...

Background: Tacrolimus is an immunosuppressant mainly used in the prophylaxis of solid organ transplant rejection. Therapeutic drug monitoring of tacrolimus is essential for avoiding toxicity related to overexposure and transplant rejection from underexposure. Previous studies suggest that unbound tacrolimus concentrations in the plasma may serve...

To the Editor: Dried blood spot (DBS)1 collection is an established sampling method for new born screening and is increasingly used in other domains, including therapeutic drug monitoring, toxicology, microbiology, and genetics. Advantages of DBS sampling are the low blood volume requirements, minimally invasive collection, favorable stability of...

OBJECTIVE To assess target attainment of busulfan exposure using a new model-based dosing regimen and therapeutic drug monitoring (TDM). Busulfan is an alkylating drug used in conditioning regimens for allogeneic haematopoietic cell transplantation (allo-HCT). Its narrow therapeutic range in combination with large interindividual variability in exp...

Case description To evaluate whether continuous intravenous (i.v.) administration of enfuvirtide (T20) could be a suitable alternative to subcutaneous (s.c.) administration of T20 in a patient with extensively drug-resistant HIV experiencing difficulties administering T20 subcutaneously. T20 was administered to a patient through 100 mL cassettes on...

The therapeutic monoclonal antibody Infliximab (IFX) is a widely used drug for the treatment of several inflammatory autoimmune diseases. However, approximately 10% of patients develop anti-infliximab antibodies (ATIs) rendering the treatment ineffective. Early detection of underexposure to unbound IFX would result in a timely switch of therapy whi...

Background: Current gentamicin dosing algorithms in adult populations target a high peak concentration (Cmax) assuring efficacy and a drug-free period (concentration <0.5 mg/L) preventing toxicity. In contrast, gentamicin-based regimens in neonatal sepsis often aim for lower peak levels and trough concentrations of 0.5-2.0 mg/L. The latter concent...

Background: To increase target attainment rates, switching the mode of administration from intermittent (InI) to continuous infusion (CoI) has been proposed. In this study target attainment rates and inter-patient variation in exposure were compared between vancomycin InI and CoI treated critically ill patients. Methods: An observational cohort...

Cyanide is een sterkwerkend gif dat in gebonden toestand voorkomt in vele zaden en planten, waaronder bittere amandelen en abrikozenpitkernen.2 Tevens is het een chemische verbinding die in de industrie en huishoudelijke producten voorkomt.3 Sinds 2006 waarschuwt de Nederlandse Voedsel- en Warenautoriteit (NVWA) voor de consumptie van deze onschuld...

Background: Barbiturate intoxication is potentially lethal. With the availability of the newer anticonvulsants the use of barbiturates in treating epilepsy has decreased significantly, with a concurrent decrease in the incidence of overdose with these medications. There have, however, been recent alarm signals from governmental sources concerning...

Annually, about 8000 heart and lung transplantations are successfully performed worldwide. However, morbidity and mortality still pose a major concern. Renal failure in heart and lung transplant recipients is an essential adverse cause of morbidity and mortality, often originating in the early postoperative phase. At this time of clinical instabili...

Both darunavir (DRV) and trimethoprim-sulfamethoxazole (TMP-SMX) carry a sulfonamide moiety and a warning for this cross-reactivity is given in the label of DRV. The aim of this study was to investigate the potential cross-reactivity between both drugs. Retrospective cohort study with a nested case-control study. HIV-infected patients that received...

Abstract Kidney injury triggers fibrosis, the final common pathway of chronic kidney disease (CKD). The increase of CKD prevalence worldwide urgently calls for new therapies. Available systemic treatment such as rapamycin are associated with serious side effects. To study the potential of local antifibrotic therapy, we administered rapamycin-loaded...

Background: hospitalized patients with serious infections treated with aminoglycosides are at risk of developing nephrotoxicity. Previous clinical studies have shown that the pharmacokinetics of aminoglycosides in humans follow a circadian rhythm. Therefore, the time of administration could have important clinical implications with respect to the...

Introduction: The clinical application of continuous infusion (CoI) of vancomycin has gained interest in recent years. Since no international guidelines on initial dosing of vancomycin CoI exist, there is a need for methods to facilitate the switch from intermittent to continuous vancomycin dosing algorithms in clinically infected populations. The...

Cyclophosphamide and vincristine are widely used intravenous chemotherapeutic agents in both human and veterinary oncology. Although intravenous administration of these chemotherapeutics is the gold standard in most treatment protocols, this route of administration has several disadvantages (e.g. long infusion times and risk of extravasation). Ther...

Busulfan (Bu) is used as a myeloablative agent in conditioning regimens prior to allogeneic haematopoietic cell transplantation (allo-HCT). In line with strategies explored in adults, the outcomes may be optimized by replacing cyclophosphamide (Cy) +/- Melphalan (Mel) with fludarabine (Flu). Therefore we compared the outcomes in two consecutive coh...

Dosing of phenytoin is difficult in children because of its variable pharmacokinetics and protein binding. Possible covariates for this protein binding have mostly been univariately investigated in small, and often adult, adult populations. We conducted a study to identify and quantify these covariates in children. We extracted data on serum phenyt...

Background: Ritonavir is an extremely strong inhibitor of P450 cytochrome 3A, which is the main metabolizing enzyme of tacrolimus. Subsequently, the pharmacokinetics of tacrolimus are affected to a large extend by the coadministration of ritonavir in HIV-infected transplant recipients. Therefore, to prevent overexposure directly posttransplantatio...

Abstract Since the introduction of combination antiretroviral therapy (cART) resulting in the prolonged survival of HIV-infected patients, HIV infection is no longer considered to be a contraindication for solid organ transplantation (SOT). The combined management of antiretroviral and immunosuppressive therapy proved to be extremely challenging, a...

Background and Aims Treatment of intentional (mainly by adolescents) and unintentional (mainly by children) intoxications with the increasingly popular drug gamma-hydroxybutyrate (GHB) primarily consists of symptomatic treatment. The usually rapid absorption and the need for intubation argue against activated charcoal (AC) treatment in GHB intoxica...

van Zeeland, Y. R. A., Schoemaker, N. J., Haritova, A., Smit, J. W., van Maarseveen, E. M., Lumeij, J. T., Fink-Gremmels, J. Pharmacokinetics of paroxetine, a selective serotonin reuptake inhibitor, in Grey parrots (Psittacus erithacus erithacus): influence of pharmaceutical formulation and length of dosing. J. vet. Pharmacol. Therap. 36, 51–58. Pa...