Hair analysis for monitoring adherence to inhaled respiratory medications: possibilities and limitations.

Purpose: Non-adherence to inhaled medication poses a significant clinical and economic burden on patients with respiratory diseases. This narrative review provides an overview of key aspects of hair analysis, in general and specific for inhaled medications, and explores the potential of hair analysis as a novel tool to monitor adherence to inhaled medications.

Methods: PubMed searches were conducted to explore four aspects: (1) mechanisms of (inhaled) drug's systemic absorption and deposition in hair; (2) quantification of drugs in hair; (3) factors impacting (inhaled) drug hair concentrations; and (4) clinical studies assessing inhaled medication adherence through hair analysis.

Osimertinib Cost Minimization in Non-Small Cell Lung Cancer (NSCLC) Treatment: Hypothesis Generation for a Population Pharmacokinetic Approach for Equivalent Dose Optimization of Osimertinib in Combination With Cobicistat.

Pharmacokinetic boosting can be a strategy to enhance osimertinib exposure and reduce treatment associated costs. The OSIBOOST trial demonstrated that it was feasible to boost low osimertinib plasma trough levels with cobicistat. The current study aims to establish the equivalent dose of cobicistat boosted osimertinib compared to osimertinib 80 mg once daily (QD) by population pharmacokinetic (popPK) modeling.

Validation of a LC-MS/MS Assay for Rapid and Simultaneous Quantification of Cobicistat and Venetoclax in Human Plasma and Serum.

Measuring cobicistat and venetoclax concentrations in human plasma and serum facilitates therapeutic drug monitoring (TDM) and pharmacokinetic (PK) boosting studies. Therefore, the objective of this study was to develop and validate a rapid LC-MS/MS analytical method for the simultaneous determination of cobicistat and venetoclax concentrations in plasma and serum. The method was validated according to EMA and FDA guidelines.

Effects of geranylgeranylacetone on diastolic and microvascular function in patients with heart failure with a preserved ejection fraction: A phase 2, randomized, placebo-controlled, crossover trial.

Aims: Heart failure with preserved ejection fraction (HFpEF) is a major healthcare burden with limited treatment options. Geranylgeranylacetone (GGA) has been shown to improve myocardial compliance and endothelial function in preclinical models. Given the mechanistic profile of GGA and established safety as an over-the-counter drug in Asia, we performed a phase 2 clinical trial in patients with HFpEF.

Effect of therapeutic plasma exchange on amoxicillin, clindamycin, midazolam, and morphine pharmacokinetics in a critically ill child.

We report a 15-year-old boy with severe septic shock and multiple organ failure, requiring intensive care and extracorporeal therapies, including veno-arterial extracorporeal membrane oxygenation, continuous veno-venous hemodiafiltration, and therapeutic plasma exchange. Given their critical role in the clinical management, pharmacokinetics of amoxicillin, clindamycin, midazolam, and morphine were closely monitored. Drug concentrations were measured before, during, and after therapeutic plasma exchange sessions.

Tacrolimus Trough Concentrations are Not Impacted by Epstein-Barr Virus Serology and Viral Load in Pediatric Liver Transplant Recipients.

Background And Objectives: Epstein-Barr virus (EBV) is a common herpesvirus among pediatric liver transplant recipients, but it can have serious complications, such as post-transplant lymphoproliferative disease. EBV is hypothesized to influence tacrolimus concentrations by increasing inflammatory cytokines that regulate the expression of cytochrome-P-450 enzymes involved in tacrolimus pharmacokinetics. This study aims to examine the association between EBV serostatus and viral load, and tacrolimus trough concentrations corrected for the dose and recipient weight [weight-adjusted concentration-to-dose (C/D) ratios].

Plasma Versus Whole Blood Tacrolimus Concentrations and Health-Related Quality of Life in Kidney Transplant Recipients.

: Tacrolimus dosing traditionally relies on therapeutic drug monitoring in whole blood, while assessment in plasma may better reflect its effect and reveal overdosing impacting health-related quality of life (HRQoL). : In this cross-sectional study, 898 kidney transplant recipients (KTRs) who were at least 12 months post-transplantation were included. Plasma and whole blood tacrolimus concentrations were compared using Passing-Bablok regression analyses and Bland-Altman plots.

Auto-Induction in Oral Esketamine Treatment for Treatment-Resistant Depression: An Exploratory Study.

Esketamine is a rapidly acting antidepressant with robust efficacy in treatment-resistant depression (TRD). Diminishing therapeutic effects and attenuated side effects have been reported after long-term use. This study aimed to investigate its long-term pharmacokinetics and factors that may contribute to reduced efficacy over time in patients with TRD by evaluating the potential role of auto-induction.

Pharmacokinetics of Ivacaftor, Tezacaftor, Elexacaftor, and Lumacaftor in Special Cystic Fibrosis Populations: A Systematic Review.

Background And Objective: Following the development of cystic fibrosis transmembrane conductance regulator (CFTR) modulators (ivacaftor, tezacaftor, elexacaftor, and lumacaftor), the prognosis for people diagnosed with cystic fibrosis (pwCF) has improved. Understanding the pharmacokinetics (PK) of CFTR modulators is crucial to provide optimal care, particularly in special cystic fibrosis (CF) populations such as pwCF with hepatic impairment, pancreatic insufficiency, those who are pregnant or lactating, or who are children. We aim to provide an overview of the PK of CFTR modulators in these populations.

Paracetamol loading dose administration in children: a retrospective study.

Objective: To determine the extent to which recommended paracetamol loading doses are administered in an academic paediatric hospital and to determine whether paracetamol loading doses are necessary to achieve the therapeutic target concentration of 10 mg/L in (pre)term neonates and children.

Methods: A retrospective study was performed including (pre)term neonates and children who were hospitalised between 1 January 2023 and 1 January 2024 and received at least one dose of intravenous or rectal paracetamol. The number of treatments with and without a paracetamol loading dose was evaluated.

Fasting and postprandial kidney haemodynamic effects of empagliflozin and linagliptin in mono- and combination therapy compared to gliclazide in overweight people with type 2 diabetes (RACELINES): A randomised, double-blind trial.

Background: Sodium-glucose cotransporter (SGLT) 2 inhibitors attenuate fasting glomerular hyperfiltration in people with type 2 diabetes (T2D). However, SGLT2-inhibition increases glucagon levels, which facilitate postprandial hyperfiltration. The impact of SGLT2 inhibition on protein-related hyperfiltration and postprandial (intra) kidney haemodynamic function is unclear.

Metamizole induces voriconazole metabolism and results in subtherapeutic voriconazole concentrations.

Aims: Voriconazole is extensively metabolized via cytochrome P450 (CYP) enzymes, predominantly CYP2C19 and CYP3A4. Drugs influencing the activity or expression of CYP enzymes can cause clinically relevant changes in the metabolism and voriconazole exposure. Metamizole is known to induce CYP3A4 and CYP2C19.

Quantification of Ivacaftor, Tezacaftor, Elexacaftor, and Lumacaftor and their active metabolites in plasma using UHPLC-MS/MS: Doors open to the application of therapeutic drug monitoring in cystic fibrosis treatment.

An ultra-high performance liquid chromatography-tandem mass spectrometry method was developed to quantify the cystic fibrosis transmembrane conductance regulator (CFTR) modulators ivacaftor, tezacaftor, elexacaftor, and lumacaftor and their active metabolites hydroxymethyl ivacaftor, tezacaftor M1, and N-desmethylelexacaftor in human EDTA plasma. The analytical method utilized protein precipitation with stable isotope dilution for sample preparation, facilitating a simple and rapid assay, with a total runtime of only 2.1 min.

Unveiling mechanisms underlying kidney function changes during sex hormone therapy.

BACKGROUNDMen with chronic kidney disease (CKD) experience faster kidney function decline than women. Studies in individuals undergoing sex hormone therapy suggest a role for sex hormones, as estimated glomerular filtration rate (eGFR) increases with feminizing therapy and decreases with masculinizing therapy. However, effects on measured GFR (mGFR), glomerular and tubular function, and involved molecular mechanisms remain unexplored.

Low-cost generation of clinical-grade, layperson-friendly pharmacogenetic passports using oligonucleotide arrays.

Pharmacogenomic (PGx) information is essential for precision medicine, enabling drug prescriptions to be personalized according to an individual's genetic background. Almost all individuals will carry a genetic marker that affects their drug response, so the ideal drug prescription for these individuals will differ from the population-level guidelines. Currently, PGx information is often not available at first prescription, reducing its effectiveness.

Tolerability and Pharmacokinetic Evaluation of Inhaled Dry Powder Tobramycin in Children with Cystic Fibrosis.

() is the predominant pulmonary pathogen in persons with Cystic Fibrosis (CF). Nebulization with tobramycin or colistin is mostly applied but has a significant treatment burden. Dry powder (DP) inhalation may offer an attractive alternative.

The Impact of Once Daily Dosing on Protein Binding of Clozapine and Norclozapine.

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.

Plasma esketamine and noresketamine levels and antidepressant response with oral esketamine treatment.

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.

Early economic evaluation of chelation therapy in kidney transplant recipients with high-normal lead.

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.

Increased ferritin levels are associated with incident diabetes after kidney transplantation: A prospective cohort study.

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.

Clinical and Biochemical Factors Associated with Infliximab Pharmacokinetics in Paediatric Patients with Inflammatory Bowel Disease.

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.

Improved real-world UHPLC-MS/MS iohexol analysis; thawed samples, improved calibration curve, and additional matrices.

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.