Background And Objective: When utilizing population pharmacokinetic (popPK) models for a priori dosage individualization, selecting the best model is crucial to obtain adequate doses. We developed and evaluated several model-selection and ensembling methods, using external evaluation on the basis of therapeutic drug monitoring (TDM) samples to identify the best (set of) models per patient for a priori dosage individualization.
Methods: PK data and models describing both hospitalized patients (n = 134) receiving continuous vancomycin (26 models) and patients (n = 92) receiving imatinib in an outpatient setting (12 models) are included.
Aims: Sunitinib exhibits considerable interindividual variability in exposure. While the target total plasma concentration of sunitinib and its active metabolite is 50-87.5 ng/mL for the intermittent dosing schedule, ~10-21% of patients experience higher exposures (>87.
View Article and Find Full Text PDFIntroduction 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.
View Article and Find Full Text PDFAims: With the rising number of oral targeted oncolytics and growing awareness of the benefits of therapeutic drug monitoring (TDM) within the field of oncology, it is expected that the requests for quantifying concentrations of these drugs will increase. It is important to (cross-)validate available assays and ensure its quality, as results may lead to altered dosing recommendations. Therefore, we aimed to evaluate the performance of laboratories measuring concentrations of targeted oral oncolytics in a one-time international quality control (QC) programme.
View Article and Find Full Text PDFImatinib plasma trough concentrations are associated with efficacy for patients treated for advanced or metastatic KIT-positive gastrointestinal stromal tumours (GISTs). This relationship has not been studied for patients treated in the neoadjuvant setting, let alone its correlation with tumour drug concentrations. In this exploratory study we aimed to determine the correlation between plasma and tumour imatinib concentrations in the neoadjuvant setting, investigate tumour imatinib distribution patterns within GISTs, and analyse its correlation with pathological response.
View Article and Find Full Text PDFPatients with cancer are prone to prolongation of the corrected QT interval (QTc) due to the use of anticancer drugs with QTc-prolonging potential in combination with electrolyte imbalances caused by, for example, gastrointestinal side-effects. However, most anticancer drugs were approved with little information on their QTc-prolonging potential and the added risk of torsade de pointes. The absence of this information on the drug label poses a considerable challenge to clinicians regarding the measures that need to be taken to safely start anticancer treatment.
View Article and Find Full Text PDFThe antipsychotic drug clozapine is associated with weight gain. The proposed mechanisms include blocking of serotonin (5-HT ), dopamine (D ) and histamine (H ) receptors. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2) to norclozapine, a metabolite with more 5-HT -receptor and less H blocking capacity.
View Article and Find Full Text PDFObjectives: To describe the cumulative incidences of adverse drug reactions (ADRs) associated with disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients from real-world data (RWD), using the DREAM-RA registry, and to compare these with incidence frequencies mentioned in the Summary of Product Characteristics (SmPC).
Methods: All ADRs in patients with recorded use of adalimumab, etanercept, hydroxychloroquine, leflunomide, oral and subcutaneous methotrexate, and sulfasalazine from a single center participating in the DREAM-RA registry (n = 1,098 patients) that were directly sent to the Netherlands Pharmacovigilance Center Lareb were assessed. Cumulative incidences were calculated, described and compared to the most recently revised SmPCs.