Dose-Limiting Toxicities of Paclitaxel in Breast Cancer Patients: Studying Interactions Between Pharmacokinetics, Physical Activity, and Body Composition-A Protocol for an Observational Cohort Study.

: Paclitaxel (PTX), a commonly used chemotherapy for breast cancer (BC), is associated with dose-limiting toxicities (DLTs) such as peripheral neuropathy and neutropenia. These toxicities frequently lead to dose reductions, treatment delays, or therapy discontinuation, negatively affecting patients' quality of life and clinical outcomes. Current dosing strategies based on body surface area (BSA) fail to account for individual variations in body composition (skeletal muscle mass (SMM) and adipose tissue (AT) mass) and physical activity (PA), which can influence drug metabolism and toxicity.

The use of population pharmacokinetics to extrapolate food effects from human adults and beagle dogs to the pediatric population illustrated with ibuprofen as a case.

Oral drug administration is the most convenient route of administration in the pediatric population. However, children are often not fasted when drugs are orally administered, hence potential food-drug interactions might occur. Most of these interactions are extrapolated from studies performed in human adults where a recommended high-fat, high-calorie meal is administered prior to drug dosing.

Real-world evidence of lisinopril in pediatric hypertension and nephroprotective management: a 10-year cohort study.

Background: Over the last 20 years, pediatric hypertension (pHTN) prevalence in Western society has risen from 3.5 to 9% due to childhood overweight, obesity, and secondary kidney and cardiological conditions. Few studies have assessed commonly used antihypertensive medication lisinopril's (ACE-inhibitor) long-term efficacy and the long-term value of renin-angiotensin-aldosterone system (RAAS) biomarkers.

Pharmacokinetics and Pharmacodynamics of Nipocalimab, a Neonatal Fc Receptor Blocker, in Healthy Japanese Volunteers.

Background And Objectives: Nipocalimab is a high-affinity, fully human, effectorless immunoglobulin G1 monoclonal antibody targeting the neonatal Fc receptor and is currently under evaluation for the treatment of rare and prevalent immunoglobulin G autoantibody-mediated and alloantibody-mediated diseases. This phase I, randomized, double-blind, placebo-controlled, single-dose escalation study in healthy Japanese volunteers (N = 24) assessed the safety, pharmacokinetics, and effect on the serum immunoglobulin G level of single doses of nipocalimab.

Methods: Volunteers were grouped into three cohorts and received intravenous nipocalimab at 10, 30, or 60 mg/kg or placebo.

Penetration of Antibiotics into Subcutaneous and Intramuscular Interstitial Fluid: A Meta-Analysis of Microdialysis Studies in Adults.

Background And Objective: The interstitial fluid of tissues is the effect site for antibiotics targeting extracellular pathogens. Microdialysis studies investigating these concentrations in muscle and subcutaneous tissue have reported notable variability in tissue penetration. This study aimed to comprehensively summarise the existing data on interstitial fluid penetration in these tissues and to identify potential factors influencing antibiotic distribution.

Model-based meta-analysis to quantify the effects of short interfering RNA therapeutics on hepatitis B surface antigen turnover in hepatitis B-infected mice.

The objective of this study was to compare the efficacy of short interfering RNA therapeutics (siRNAs) in reducing hepatitis B surface antigen (HBsAg) levels in hepatitis B-infected (HBV) mice across multiple siRNA therapeutic classes using model-based meta-analysis (MBMA) techniques. Literature data from 10 studies in HBV-infected mice were pooled, including 13 siRNAs, formulated as liposomal nanoparticles (LNPs) or conjugated to either cholesterol (chol) or N-acetylgalactosamine (GalNAc). Time course of the baseline- and placebo-corrected mean HBsAg profiles were modeled using kinetics of drug effect (KPD) model coupled to an indirect response model (IRM) within a longitudinal non-linear mixed-effects MBMA framework.

Combination Therapy With Guselkumab and Golimumab in Patients With Moderately to Severely Active Ulcerative Colitis: Pharmacokinetics, Immunogenicity and Drug-Drug Interactions.

A proof-of-concept study with the combination of guselkumab and golimumab in patients with ulcerative colitis (UC) has shown that the combination therapy resulted in greater efficacy than the individual monotherapies. The current analysis evaluated the pharmacokinetics (PK) and immunogenicity of guselkumab and golimumab in both the combination therapy and individual monotherapies. Blood samples were collected to evaluate serum concentrations and immunogenicity of guselkumab and golimumab.

Pharmacokinetics and pharmacodynamics across infusion rates of intravenously administered nipocalimab: results of a phase 1, placebo-controlled study.

Introduction: Nipocalimab is a high-affinity, fully human, aglycosylated, effectorless, immunoglobulin G (IgG) 1 monoclonal antibody that targets the neonatal Fc receptor (FcRn), decreases systemic IgG including autoantibodies, and is under development in several IgG autoantibody- and alloantibody-mediated diseases, including generalized myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, maternal-fetal medicine, and multiple other therapeutic areas. An initial phase 1 study with single and multiple ascending doses of nipocalimab infused intravenously (IV) over 2 h demonstrated dose-dependent serum pharmacokinetics and IgG reductions, with an adverse event (AE) profile comparable to placebo.

Methods: The current investigation evaluates the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of nipocalimab across various IV infusion rates in a randomized, double-blind, placebo-controlled, sequential-dose study.

The Use of Population Pharmacokinetics to Extrapolate Food Effects from Human Adults and Beagle Dogs to the Pediatric Population Illustrated with Paracetamol as a Test Case.

To date, food-drug interactions in the pediatric population remain understudied. The current food effect studies are mostly performed in adults and do not mimic the real-life situation in the pediatric population. Since the potential benefits of food effect studies performed in pediatrics should be counterbalanced with the burden that these studies pose to the patients, alternative research strategies should be evaluated.

Development and validation of an UPLC-MS/MS method for the determination of irinotecan (CPT-11), SN-38 and SN-38 glucuronide in human plasma and peritoneal tumor tissue from patients with peritoneal carcinomatosis.

Irinotecan (CPT-11), an antineoplastic drug, is used for the treatment of colorectal and pancreatic cancer due to its topoisomerase I inhibitory activity. CPT-11 is a prodrug which is converted to its active metabolite SN-38 by carboxylesterases. SN-38 is further metabolized to its inactive metabolite SN-38 glucuronide.

Prevalence and growth potential of Listeria monocytogenes in innovative, pre-packed, plant-based ready-to-eat food products on the Belgian market.

In recent years, pre-packed ready-to-eat (RTE) food products on the Belgian market have shifted to a more plant-based composition due to a variety of reasons, including consumer concerns about health, animal welfare, and sustainability. However, similar to animal-based RTE foods, plant-based RTE foods can be susceptible to the presence and outgrowth of Listeria monocytogenes (L. monocytogenes).

Population pharmacokinetics of lisinopril in hypertensive children and adolescents with normal to mildly reduced kidney function.

Aims: Lisinopril, an angiotensin-converting enzyme inhibitor, is a frequently prescribed antihypertensive drug in the paediatric population, while being used off-label under the age of 6 years in the USA and for all paediatric patients globally. The SAFEPEDRUG project (IWT-130033) investigated lisinopril pharmacokinetics in hypertensive paediatric patients corresponding with the day-to-day clinical population.

Methods: The dose-escalation pilot study included 13 children with primary and secondary hypertension who received oral lisinopril once daily in the morning; doses ranged from 0.

CO-Driven Nebulization of pH-Sensitive Supramolecular Polymers for Intraperitoneal Hydrogel Formation and the Treatment of Peritoneal Metastasis.

Because peritoneal metastasis (PM) from ovarian cancer is characterized by non-specific symptoms, it is often diagnosed at advanced stages. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) can be considered a promising drug delivery method for unresectable PM. Currently, the efficacy of intraperitoneal (IP) drug delivery is limited by the off-label use of IV chemotherapeutic solutions, which are rapidly cleared from the IP cavity.

Predicting Volume of Distribution in Neonates: Performance of Physiologically Based Pharmacokinetic Modelling.

The volume of distribution at steady state (Vss) in neonates is still often estimated through isometric scaling from adult values, disregarding developmental changes beyond body weight. This study aimed to compare the accuracy of two physiologically based pharmacokinetic (PBPK) Vss prediction methods in neonates (Poulin & Theil with Berezhkovskiy correction (P&T+) and Rodgers & Rowland (R&R)) with isometrical scaling. PBPK models were developed for 24 drugs using in-vitro and in-silico data.

Translation Arrest: A Key Player in Plant Antiviral Response.

Plants evolved several mechanisms to protect themselves against viruses. Besides recessive resistance, where compatible host factors required for viral proliferation are absent or incompatible, there are (at least) two types of inducible antiviral immunity: RNA silencing (RNAi) and immune responses mounted upon activation of nucleotide-binding domain leucine-rich repeat (NLR) receptors. RNAi is associated with viral symptom recovery through translational repression and transcript degradation following recognition of viral double-stranded RNA produced during infection.

Poikilocytosis of Angora goats is associated with erythrocyte density and reticulocytosis.

Angora goats in South Africa experience several syndromes that result in notable morbidity and mortality in juveniles and adults, but not kids. Insight into their causes is hampered by the lack of normal reference values for this breed, and the present study therefore aimed to characterise (1) differences in the haematology of healthy kids at birth and weaning, and (2) the haematology of apparently healthy yearlings. Selected variables were measured by blood smear analysis, and complete blood counts were performed using an ADVIA 2120i.

Capability of Children with Hearing Devices: A Mixed Methods Study.

We investigated 34 deaf and hard-of-hearing children with hearing devices aged 8-12 years and 30 typical hearing peers. We used the capability approach to assess well-being in both groups through interviews. Capability is "the real freedom people have to do and to be what they have reason to value.

Acute balenine supplementation in humans as a natural carnosinase-resistant alternative to carnosine.

Balenine possesses some of carnosine's and anserine's functions, yet it appears more resistant to the hydrolysing CN1 enzyme. The aim of this study was to elucidate the stability of balenine in the systemic circulation and its bioavailability in humans following acute supplementation. Two experiments were conducted in which (in vitro) carnosine, anserine and balenine were added to plasma to compare degradation profiles and (in vivo) three increasing doses (1-4-10 mg/kg) of balenine were acutely administered to 6 human volunteers.

Thraustochytrid hosts for expression of proteins relevant to SARS-CoV-2 intervention.

The emergence of COVID-19 as a global pandemic had sharply illustrated the limitations of research and development pipelines and scaled manufacturing. Although existing vaccines were created in record time, global deployment remains limited by regional production scales. Similarly, the most effective treatments for infected COVID-19 patients are also constrained by production scales as well as by the cost of production and thus expense per treatment.

Building a Human Physiologically Based Pharmacokinetic Model for Aflatoxin B1 to Simulate Interactions with Drugs.

Mycotoxins such as aflatoxin B1 (AFB1) are secondary fungal metabolites present in food commodities and part of one's daily exposure, especially in certain regions, e.g., sub-Saharan Africa.