Removal of psychotropic drugs by hemoadsorption with the HA380 cartridge.

Introduction: Psychotropic drug intoxication may require urgent management. Hemoadsorption (HA) may detoxify blood in such cases, but its effect has not been quantified.

Methods: We studied in-vivo removal of valproate, quetiapine and escitalopram with HA using the Jafron HA 380 cartridge in six sheep.

A comparison between venous blood sampling and capillary volumetric absorptive microsampling for antibiotics levels monitoring in individuals with and without periodontal disease.

Objectives: We aimed to compare the antibiotic concentrations obtained using the volumetric absorptive microsampling (VAMS) devices with those determined in plasma from conventional venous blood collected within the frame of a pharmacokinetic study of amoxicillin (AMO), metronidazole (MET), azithromycin (AZI), commonly used for periodontal treatment. The suitability and overall, acceptability of the VAMS approach was also ascertained by both participants of the pilot study and dentist practitioners.

Materials And Methods: Twelve volunteers (6 subjects without periodontal problems (PH), and 6 individuals affected with periodontitis (PP)) were administered 500 mg each of amoxicillin, metronidazole, and azithromycin.

Pharmacokinetics of levosimendan in critically Ill children on extracorporeal membrane oxygenation: a prospective observational study.

Background: Levosimendan is used off-label in pediatrics and pharmacokinetic (PK) data in this population are scarce. The only study in critically ill patients on extracorporeal membrane oxygenation (ECMO) showed altered PK parameters. Our study aimed to characterize the PK profile of levosimendan and its metabolites in critically ill children on ECMO and assess the adequacy of current dosing practices.

Is the salivary concentration of lamotrigine and levetiracetam associated with clinical outcome?

Introduction: The correlation between plasma and saliva concentration of anti-seizure medication (ASM) is well established, but variability limits the acceptance of saliva-based Therapeutic Drug Monitoring (TDM). We analysed the correlation between salivary levetiracetam and lamotrigine levels, and efficacy and tolerability.

Methods: Blood and saliva samples were collected over two years.

A Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantification of Cystic Fibrosis Drugs (Caftors) in Plasma and Its Application for Therapeutic Monitoring.

Cystic fibrosis (CF) is a life-threatening disorder caused by mutations in the CFTR gene, leading to defective chloride ion transport and thickened mucus in the respiratory and gastrointestinal systems. CFTR modulators, including ivacaftor, lumacaftor, tezacaftor, and elexacaftor, have improved patient outcomes, but interindividual pharmacokinetic variability and potential drug-drug interactions require therapeutic drug monitoring (TDM) for optimal efficacy and safety. In this context, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous quantification of CFTR modulators and their major active metabolites in human plasma to support pharmacokinetic studies and routine TDM.

Population-Based Prevalence of Antibiotic Residuals in Low, Moderate and High Malaria Endemicity Areas in Tanzania.

Background: Inappropriate antibiotic use drives antimicrobial resistance and remains a global concern. Evidence suggests antibiotic use may be higher among malaria-negative patients compared to malaria-positive ones, but uncertainty persists, particularly in regions with varying malaria prevalence. This study measured antibiotic residuals in three Tanzanian regions with varying malaria epidemiology and analyzed factors influencing their presence.

Removal of Ticagrelor by Hemoadsorption with the HA380 Cartridge.

Introduction: Hemoadsorption has emerged as a potential intervention for the removal of ticagrelor. We aimed to evaluate the efficacy of the HA380 hemoadsorption cartridge for this purpose.

Methods: Six healthy adult sheep received 270 mg of ticagrelor via an orogastric tube, followed by hemoadsorption using a HA380 cartridge for a duration of 4 h.

Clinical value of saliva therapeutic drug monitoring of newer antiseizure medications.

Introduction: Saliva is a promising option for therapeutic drug monitoring, with studies since the 1970s indicating a good correlation between plasma and saliva levels for early anti-seizure medications, although limited data exist for newer generation drugs.

Objectives: To evaluate the reliability and predictive power of saliva as a minimally invasive surrogate marker of plasma concentration for the routine therapeutic drug monitoring (TDM) of newer anti-seizure medications (ASM).

Methods: We collected blood samples at steady state in patients at least 6 h post-dose, paired with unstimulated saliva samples.

Individualization of piperacillin dosage based on therapeutic drug monitoring with or without model-informed precision dosing: a scenario analysis.

Background: Model-informed precision dosing (MIPD) combines population pharmacokinetic knowledge with therapeutic drug monitoring (TDM) to optimize dosage adjustment. It could improve target concentration attainment over empirical TDM, still widely practised for broad-spectrum antibiotics.

Objectives: To evaluate the respective performance of TDM and MIPD in achieving target piperacillin exposure.

Highly sensitive ultra-high-performance liquid chromatography coupled with tandem mass spectrometry method for the multiplex analysis of levosimendan and its metabolites OR-1855 and OR-1896 in human plasma.

Levosimendan is a positive inotrope and vasodilator used in patients with acute and chronic decompensated heart failure. It is metabolized into OR-1855 (inactive metabolite), which is further acetylated into OR-1896 (active metabolite having a prolonged half-life, hence a sustained effect). Levosimendan represents a valuable alternative to traditional inotropes with broad clinical applications in critically ill patients with cardiogenic shock, advanced heart failure and post-cardiac surgery.

Antibacterial and antifungal drug concentrations in intra-abdominal abscesses: a prospective clinical study.

Secondary peritonitis with intra-abdominal abscesses (IAA) is difficult to treat because of the supposed low rate of penetration of antimicrobial drugs at the site of infection. However, clinical data about the actual bioavailability of antimicrobial drugs in IAA are scarce. This prospective observational study aimed at assessing the drug penetration in IAA of the antibiotics (piperacillin-tazobactam, carbapenems) and antifungals (fluconazole, echinocandins) that are usually recommended for the treatment of intra-abdominal infections.

Importance of Sex-Dependent Differences for Dosing Selection and Optimization of Chemotherapeutic Drugs.

Background: Despite major advances in cancer treatment in the past years, there is a need to optimize chemotherapeutic drug dosing strategies to reduce toxicities, suboptimal responses, and the risk of relapse. Most cancer drugs have a narrow therapeutic index with substantial pharmacokinetics variability. Yet, current dosing approaches do not fully account for the complex pathophysiological characteristics of the patients.

Removal of Meropenem and Piperacillin during Experimental Hemoadsorption with the HA380 Cartridge.

Introduction: Hemoadsorption can be used as adjunctive therapy for sepsis. However, there is limited evidence regarding its antibiotic removal. In this in vivo preclinical study, we aimed to evaluate the removal of meropenem and piperacillin with the HA380 hemoadsorption cartridge.

Population Pharmacokinetics of Trametinib and Impact of Nonadherence on Drug Exposure in Oncology Patients as Part of the Optimizing Oral Targeted Anticancer Therapies Study.

Trametinib is a targeted therapy used for the treatment of solid tumours, with significant variability reported in real-life studies. This variability increases the risk of suboptimal exposure, which can lead to treatment failure or increased toxicity. Using model-based simulation, this study aims to characterize and investigate the pharmacokinetics and the adequacy of the currently recommended doses of trametinib.

Antifungal drug penetration in soft tissue abscesses: a comparative analysis.

Background: Invasive fungal infections (IFIs) are severe and difficult-to-treat infections affecting immunocompromised patients. Antifungal drug penetration at the site of infection is critical for outcome and may be difficult to achieve. Data about antifungal drug distribution in infected human tissues under real circumstances of IFI are scarce.

Prevalence and predictors of residual antibiotics in children's blood in community settings in Tanzania.

Objectives: Children account for a significant proportion of antibiotic consumption in low- and middle-income countries, with overuse occurring in formal and informal health sectors. This study assessed the prevalence and predictors of residual antibiotics in the blood of children in the Mbeya and Morogoro regions of Tanzania.

Methods: The cross-sectional community-based survey used two-stage cluster sampling to include children aged under 15 years.

Population Pharmacokinetics of Cabotegravir Following Oral Administration and Long-Acting Intramuscular Injection in Real-World People with HIV.

Long-acting cabotegravir has been studied mainly in the stringent framework of clinical trials, which does not necessarily reflect the situation of people with HIV (PWH) in routine clinical settings. The present population pharmacokinetic analysis aims to build real-world reference percentile curves of cabotegravir concentrations, accounting for patient-related factors that may affect cabotegravir exposure. The second objective is to simulate whether dosing interval adjustments of cabotegravir could be considered in specific subpopulations.

Guidance for the Interpretation of Long-Acting Cabotegravir and Rilpivirine Concentrations Based on Real-World Therapeutic Drug Monitoring Data and Documented Failures.

The interpretation of long-acting cabotegravir and rilpivirine concentrations is complicated by the lack of consensus on the threshold to consider. Building on real-world therapeutic drug monitoring data and documented virologic failures, this article provides a reappraisal of the existing thresholds and guidance for the interpretation of cabotegravir and rilpivirine concentrations.

Real-world trough concentrations and effectiveness of long-acting cabotegravir and rilpivirine: a multicenter prospective observational study in Switzerland.

Background: The efficacy and tolerability of long-acting cabotegravir and rilpivirine were demonstrated in Phase III trials. However, low concentrations combined with other risk factors have been associated with an increased risk of virologic failure. This study aims to verify whether drug concentrations measured in a real-world setting are consistent with those previously reported.

A Single-Run HPLC-MS Multiplex Assay for Therapeutic Drug Monitoring of Relevant First- and Second-Line Antibiotics in the Treatment of Drug-Resistant Tuberculosis.

The treatment of drug-resistant relies on complex antibiotic therapy. Inadequate antibiotic exposure can lead to treatment failure, acquired drug resistance, and an increased risk of adverse events. Therapeutic drug monitoring (TDM) can be used to optimize the antibiotic exposure.

Population pharmacokinetic analysis of doravirine in real-world people with HIV.

Aims: The pharmacokinetics of doravirine has been studied in clinical trials but not in real-world settings. Our study aims to characterize and identify factors influencing doravirine (a CYP3A4 substrate) pharmacokinetics in real-world people with HIV (PWH).

Methods: A total of 174 doravirine concentrations measured in 146 PWH followed up in the therapeutic drug monitoring (TDM) program at the University Hospital of Lausanne (Switzerland) between 2019 and 2023 were included in the analysis.

Development and validation of a multiplex HPLC-MS/MS assay for the monitoring of JAK inhibitors in patient plasma.

Janus kinase inhibitors (JAKi) are oral small molecules used in the treatment of a broad spectrum of autoimmune and myeloproliferative diseases. JAKi exhibit significant intra- and inter-individual pharmacokinetic variabilities, due to fluctuations in compliance with oral treatments and their metabolism essentially driven by cytochrome P450 enzymes. Intrinsically, JAKi have dose-response relationship and narrow therapeutic index: therapeutic drug monitoring (TDM) is expected to optimize and adapt their dosage regimen in order to resolve problems of efficacy and tolerance linked to dose and safety.