Validation of a method for the determination of Aderamastat (FP-025) in KEDTA human plasma by LC-MS/MS.

Aderamastat (FP-025) is a small molecule, selective matrix metalloproteinase (MMP)-12 inhibitor, under development for respiratory conditions which may include chronic inflammatory airway diseases and pulmonary fibrosis. To support evaluation of the pharmacokinetic parameters of Aderamastat in humans, we developed and validated a high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) analytical method for the quantification of Aderamastat in human plasma. This assay was validated in compliance with the Food and Drug Administration (FDA) Good Laboratory Practice Regulations (GLP) and European Medicines Agency (EMA) guidelines.

Monoclonal antibody biosimilars for cancer treatment.

Monoclonal antibodies are important cancer medicines. The European Medicines Agency (EMA) approved 48 and the Food and Drug Administration (FDA) 56 anticancer monoclonal antibody-based therapies. Their high prices burden healthcare systems and hamper global drug access.

Infliximab in paediatric inflammatory bowel disease: External evaluation of population pharmacokinetic models.

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.

Validation of an LC-MS/MS assay for rapid and simultaneous quantification of 21 kinase inhibitors in human plasma and serum for therapeutic drug monitoring.

Kinase inhibitors have revolutionized cancer treatment in the past 25 years and currently form the cornerstone of many treatments. Due to the increasing evidence for therapeutic drug monitoring (TDM) of kinase inhibitors, the need is growing for new assays to rapidly evaluate kinase inhibitor plasma concentrations. In this study, we developed an LC-MS/MS assay for the rapid and simultaneous quantification of 21 kinase inhibitors.

Clinical Validation of a Capillary Blood Home-Based Self-Sampling Technique for Monitoring of Infliximab, Vedolizumab, and C-Reactive Protein Concentrations in Patients With Inflammatory Bowel Disease.

Background: Therapeutic drug monitoring provides important guidance for treatment of patients with inflammatory bowel disease (IBD) and could help to early identify treatment failure. This study aimed to validate a finger prick-based capillary blood sampling technique to measure biological trough levels and C-reactive protein (CRP) and evaluate patient performance and -support.

Methods: In this prospective cohort study, patients with IBD receiving infliximab (IFX) or vedolizumab (VEDO) therapy performed finger prick-based capillary blood sampling at home.

Capsules with Ileocolonic-Targeted Release of Vitamin B, B, and C (ColoVit) Intended for Optimization of Gut Health: Development and Validation of the Production Process.

The ileocolonic-targeted delivery of vitamins can establish beneficial alterations in gut microbial composition. Here, we describe the development of capsules containing riboflavin, nicotinic acid, and ascorbic acid covered with a pH-sensitive coating (ColoVit) to establish site-specific release in the ileocolon. Ingredient properties (particle size distribution, morphology) relevant for formulation and product quality were determined.

Pharmacokinetic Boosting of Kinase Inhibitors.

(1) Introduction: Pharmacokinetic boosting of kinase inhibitors can be a strategy to enhance drug exposure and to reduce dose and associated treatment costs. Most kinase inhibitors are predominantly metabolized by CYP3A4, enabling boosting using CYP3A4 inhibition. Kinase inhibitors with food enhanced absorption can be boosted using food optimized intake schedules.

The Pharmacokinetics and Target Attainment of Antimicrobial Drugs Throughout Pregnancy: Part III Non-penicillin and Non-cephalosporin Drugs.

Introduction: Understanding the pharmacokinetics (PK) of antimicrobial drugs in pregnant women is crucial to provide effective and safe treatment. This study is part of a series that systematically reviews literature on the PK and analyzes if, based on the changed PK, evidence-based dosing regimens have been developed for adequate target attainment in pregnant women. This part focusses on antimicrobials other than penicillins and cephalosporins.

Pharmacokinetics and Target Attainment of Antimicrobial Drugs Throughout Pregnancy: Part I-Penicillins.

Background And Objective: Pharmacokinetics (PK) are severely altered in pregnant women due to changes in volume of distribution (Vd) and/or drug clearance (CL), affecting target attainment of antibiotics in pregnant women. This review is part of a series that reviews literature on the description of PK and target attainment of antibiotics in pregnant women with specific focus on penicillins.

Methods: A systematic literature search was carried out in PubMed.

Therapeutic drug monitoring-guided treatment versus standard dosing of voriconazole for invasive aspergillosis in haematological patients: a multicentre, prospective, cluster randomised, crossover clinical trial.

Objectives: Voriconazole therapeutic drug monitoring (TDM) is recommended based on retrospective data and limited prospective studies. This study aimed to investigate whether TDM-guided voriconazole treatment is superior to standard treatment for invasive aspergillosis.

Methods: A multicentre (n = 10), prospective, cluster randomised, crossover clinical trial was performed in haematological patients aged ≥18 years treated with voriconazole.

Timely administration of tocilizumab improves outcome of hospitalized COVID-19 patients.

Introduction: The aim of this study was to determine the efficacy of early tocilizumab treatment for hospitalized patients with COVID-19 disease.

Methods: Open-label randomized phase II clinical trial investigating tocilizumab in patients with proven COVID-19 admitted to the general ward and in need of supplemental oxygen. The primary endpoint of the study was 30-day mortality with a prespecified 2-sided significance level of α = 0.

Population Pharmacokinetic Modelling and Limited Sampling Strategies for Therapeutic Drug Monitoring of Pyrazinamide in Patients with Tuberculosis.

Pyrazinamide is one of the first-line antituberculosis drugs. The efficacy of pyrazinamide is associated with the ratio of 24-h area under the concentration-time curve (AUC) to MIC. The objective of this study was to develop and validate a limited sampling strategy (LSS) based on a population pharmacokinetic (popPK) model to predict AUC.

Population pharmacokinetic model and limited sampling strategy for clozapine using plasma and dried blood spot samples.

Background: To improve efficacy, therapeutic drug monitoring is often used in clozapine therapy. Trough level monitoring is regular, but trough levels provide limited information about the pharmacokinetics of clozapine and exposure in time. The area under the concentration time curve (AUC) is generally valued as better marker of drug exposure in time but calculating AUC needs multiple sampling.

Improving the aseptic transfer procedures in hospital pharmacies part C: evaluation and redesign of the transfer process.

Objectives: To transfer sterile medical devices (SMD), infusion bags (IB), ampoules (A), injection vials (V) and infusion bottles (B) into a laminar airflow cabinet (LAF) or safety cabinet (SC) with a surface bioburden as low as possible.

Methods: Surface bioburden of the outer layer of SMD, IB, A, V and B was determined by contact plates. Surface bioburden determination of critical spots on A, V and B (ampoule necks and stoppers) was determined by high-recovery swabs and contact plates.

Association between TNF Receptors and KIM-1 with Kidney Outcomes in Early-Stage Diabetic Kidney Disease.

Background And Objectives: Clinical trials in nephrology are enriched for patients with micro- or macroalbuminuria to enroll patients at risk of kidney failure. However, patients with normoalbuminuria can also progress to kidney failure. TNF receptor-1, TNF receptor-2, and kidney injury marker-1 (KIM-1) are known to be associated with kidney disease progression in patients with micro- or macroalbuminuria.

Improving the aseptic transfer procedures in hospital pharmacies. Part B: evaluation of disinfection methods for materials with a non-sterile surface.

Objectives: To improve the disinfection methods for materials with a non-sterile surface to be used in aseptic handling.

Methods: The surface bioburden on ampoules (A) and injection vials (IV) is determined by contact plates and total immersion. The occurrence of spore-forming bacteria is determined by strain colouring and matrix-assisted laser desorption ionisation-time of flight mass spectrometry.

Safe use of radiopharmaceuticals in patients with chronic kidney disease: a systematic review.

Background: Patients with chronic kidney disease (CKD) may need to have their radiopharmaceutical dosage adjusted to prevent adverse effects and poor outcomes, but there are few recommendations on radiopharmaceutical dosing for this group of patients. The aim of this study is to provide an overview of the available information on radiopharmaceutical dose recommendations for patients with CKD.

Methods: We performed a systematic literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Optimization of Fluconazole Dosing for the Prevention and Treatment of Invasive Candidiasis Based on the Pharmacokinetics of Fluconazole in Critically Ill Patients.

The efficacy of fluconazole is related to the area under the plasma concentration-time curve (AUC) over the MIC of the microorganism. Physiological changes in critically ill patients may affect the exposure of fluconazole, and therefore dosing adjustments might be needed. The aim of this study was to evaluate variability in fluconazole drug concentration in intensive care unit (ICU) patients and to develop a pharmacokinetic model to support personalized fluconazole dosing.

Improving the aseptic transfer procedures in hospital pharmacies part A: methods for the determination of the surface bioburden on ampoules and vials.

Objectives: To develop methods for surface bioburden determination of ampoules and vials to be used in the validation of the disinfection procedures and in routine monitoring of ampoules and vials.

Methods: The surface bioburdens of ampoules and vials are determined before and after disinfection by contact plates and total immersion.

Results: The mean surface bioburdens of non-disinfected ampoules and vials taken straight from the original boxes are 2.

First-in-Human Phase I Clinical Trial of an SFV-Based RNA Replicon Cancer Vaccine against HPV-Induced Cancers.

A first-in-human phase I trial of Vvax001, an alphavirus-based therapeutic cancer vaccine against human papillomavirus (HPV)-induced cancers was performed assessing immunological activity, safety, and tolerability. Vvax001 consists of replication-incompetent Semliki Forest virus replicon particles encoding HPV16-derived antigens E6 and E7. Twelve participants with a history of cervical intraepithelial neoplasia were included.

Patient-Reported Adverse Events of Radiopharmaceuticals: A Prospective Study of 1002 Patients.

Introduction: Adverse events of radiopharmaceuticals may be underreported or remain undetected. Patients can provide information about these adverse events to enable healthcare professionals to detect, understand, and manage them more efficiently.

Objective: In this study, we aimed to (a) determine the type, causality, and frequency of patient-reported adverse events of radiopharmaceuticals and to (b) assess the onset, outcome, and follow-up of these adverse events from the patient's perspective.

Discontinuation of metformin to prevent metformin-induced high colonic FDG uptake: is 48 h sufficient?

Objective: In this retrospective, single-center observational study, we investigated whether discontinuing metformin for at least 48 h prevents metformin-induced [F]fluorodeoxyglucose (FDG) uptake in all segments of the colon.

Methods: Patients with type 2 diabetes who were using metformin before undergoing an FDG PET/CT scan were included. Two groups were created: patients who discontinued metformin for less than 48 h (< 48 h group) and patients who discontinued metformin for between 48 and 72 h (≥ 48 h group).