Pharmacokinetics of Subcutaneous and Intravenous Ceftriaxone in an Older Population: The PhASAge Study.

Background: Ceftriaxone is frequently administered subcutaneously in France, especially in older patients, although this practice is currently off-label. This work aims to describe the pharmacokinetics (PK) and pharmacodynamics (PD) and tolerance of ceftriaxone administered by intravenous and subcutaneous routes in older patients.

Methods: Patients aged ≥65 years receiving intravenous or subcutaneous ceftriaxone 1 g every 24 hours were included.

Rapid quantification of 21 antihypertensive and diuretic drugs in plasma by UPLC-MS/MS: Application to clinical and forensic cases.

Systemic arterial hypertension, affecting more than 1 billion people worldwide, necessitates widespread use of antihypertensive and diuretic medications. However, the potential toxicity related to exposure of these medications is not always fully understood, potentially leading to underestimates of deaths related to cardiovascular drugs. Additionally, the growing interest in monitoring adherence to antihypertensive medications necessitates the development of specific analytical methods suitable for both clinical and forensic applications.

Underreporting of synthetic cathinone poisoning with clinical immunoassays: An experimental and observational study.

BackgroundThere is an increasing global concern about the use of synthetic cathinones (SCs). Detecting these drugs in human urine samples can be difficult, particularly in emergency settings. Cross-reactivity has been described for several immunoassays.

Impact of tacrolimus on interferon gamma ELISpot assay results for the assessment of T-cell immunity: Proof-of-concept.

SOT patients require immunosuppressors to avoid graft rejection. Therapeutic drug monitoring is insufficient to find the optimal balance with immunosuppression. The evaluation of cell-mediated immunity by enzyme-linked immunospot (ELISpot) assay enumerating interferon-gamma (IFN-γ) is increasingly use.

Biliary diffusion and antifungal activity of caspofungin and fluconazole in liver transplant recipients: A pilot study.

Invasive candidiasis, including intra-abdominal candidiasis (IAC), is a common complication after liver transplantation. Antifungal drugs such as echinocandins and fluconazole (FCZ) are frequently used to prevent or treat such fungal infections. The diffusion of these antifungals within abdominal body sites has been rarely reported, in particular, in liver transplant recipients.

A Population Pharmacokinetic Model of Tocilizumab in Kidney Transplant Patients Treated for Chronic Active Antibody-Mediated Rejection: Comparison of Plasma Exposure Between Intravenous and Subcutaneous Administration Schemes.

Background: Tocilizumab prevents the clinical worsening of chronic active antibody-mediated rejection (CAAMR) in kidney transplant recipients. Following a global shortage of the intravenous pharmaceutical form in 2022, patients were switched from monthly intravenous administration of 8 mg/kg to weekly subcutaneous injection of 162 mg, raising the question of bioequivalence between these schemes of administration.

Aims: We aimed to compare the areas under the curve (AUC) of tocilizumab in virtual simulations of populations treated with the two administration schemes and to identify the covariates that could contribute to pharmacokinetic variability of tocilizumab in kidney transplant patients with CAAMR who received tocilizumab as salvage treatment.

Early Exposure of Kidney Transplant Recipients with Chronic Antibody-Mediated Rejection to Tocilizumab-A Preliminary Study.

Tocilizumab prevents clinical worsening of chronic antibody-mediated rejection (CAMR) of kidney transplant recipients. Optimization of this treatment is necessary. We identified the determinants of early tocilizumab exposure (within the first three months) and investigated the relationship between early plasma tocilizumab exposure and graft function.

A Minimal PBPK Model for Plasma and Cerebrospinal Fluid Pharmacokinetics of Trastuzumab after Intracerebroventricular Administration in Patients with HER2-Positive Brain Metastatic Localizations.

Background: Dosing regimens of trastuzumab administered by intracerebroventricular (icv) route to patients with HER2-positive brain localizations remain empirical. The objectives of this study were to describe pharmacokinetics (PK) of trastuzumab in human plasma and cerebrospinal fluid (CSF) after simultaneous icv and intravenous (iv) administration using a minimal physiologically-based pharmacokinetic model (mPBPK) and to perform simulations of alternative dosing regimens to achieve therapeutic concentrations in CSF.

Methods: Plasma and CSF PK data were collected in two patients with HER2-positive brain localizations.

Trends in drivers testing positive for drugs of abuse in oral fluid from 2018 to 2021 in France.

Background: Driving under the influence of drugs (DUID) is a risk factor for traffic accidents. The testing of oral fluid by roadside immunochromatography and laboratory-confirmed chromatography coupled to mass spectrometry (LC-MS/MS) analysis to detect drug abuse has increased in France. The aim of this study was to describe the trends observed in drivers testing positive for illicit drugs in oral fluid and to investigate the concordance between the two analytical methods used.

NPAideS: a drug-checking study among 3-methylmethcathinone (3-MMC) users.

Background: 3-methylmethcathinone (3-MMC) has been available on the European drug market for several years, but an increase in its availability seems to have occurred around 2020, associated with reports of harm and death. We aimed to analyze the composition of the supposed 3-MMC samples purchased and its concordance with the assumed composition of the drug.

Methods: A prospective multicenter (n = 6) study was conducted between February 2021 and September 2021 in Auvergne-Rhone-Alpes, France.

Discrepancies between dihydropyrimidine dehydrogenase phenotyping and genotyping: What are the explanatory factors?

Aim: Dihydropyrimidine dehydrogenase (DPD) deficiency can be detected by phenotyping (measurement of plasma uracil [U], with U ≥ 16 μg/L defining a partial deficiency) and/or by genotyping (screening for the four most frequent DPYD variants). We aimed to determine the proportion of discrepancies between phenotypic and genotypic approaches and to identify possible explanatory factors.

Methods: Data from patients who underwent both phenotyping and genotyping were retrospectively collected.

Quantification of belatacept by liquid chromatography-tandem mass spectrometry in human plasma: Application to a pharmacokinetic study in renal transplant recipients.

Therapeutic drug monitoring is the cornerstone of immunosuppressive treatment in transplantation. The immunosuppressive drugs used in kidney transplant patients are mostly comprised of biologics, including therapeutic monoclonal antibodies (mAbs) and fusion proteins. Therefore, a specific and sensitive analytical technique that can universally quantify mAbs, as well as fusion proteins, is essential for clinical pharmacokinetics studies.

Variability of Isavuconazole Trough Concentrations during Longitudinal Therapeutic Drug Monitoring.

Isavuconazole (ISA), a triazole antifungal agent, is licensed for the treatment of invasive aspergillosis and mucormycosis. Therapeutic drug monitoring (TDM) is a cornerstone of treatment efficacy for triazole antifungals due to their pharmacokinetic variability, except for ISA, for which the utility of TDM is still uncertain. We performed a retrospective study that aimed to assess the inter- and intra-individual variability of ISA trough concentrations (Cmin) and to identify the determinants involved in such variability.

Implementation of a Vancomycin Dose-Optimization Protocol in Neonates: Impact on Vancomycin Exposure, Biological Parameters, and Clinical Outcomes.

Vancomycin dosing used in neonates results frequently in insufficient concentrations. A vancomycin dose-optimization protocol consisting of an individualization of loading and maintenance doses (administered during continuous infusion) through a previously validated pharmacokinetic model was implemented in our center. This monocenter retrospective study aimed to compare vancomycin average concentration (Cavg) in the therapeutic range (15 to 25 mg/L) and biological and clinical parameters before and after implementation of this protocol.

Tocilizumab Trough Levels Variability in Kidney-Transplant Candidates Undergoing Desensitization.

The presence of anti-HLA antibodies is an increasing challenge in kidney transplantation. Tocilizumab (TCZ), a monoclonal antibody targeting the interleukin-6 receptor (IL-6R), has been proposed to complement conventional desensitization therapy. We aimed to describe TCZ plasma trough concentrations and their variability and to investigate the link between TCZ concentration and the evolution of anti-HLA antibodies.

COVID-19 lockdowns and incidence of psychoactive substance exposure according to age and sex.

Background: The lockdown periods imposed in 2020 by governments had deleterious consequences on population mental health. Several studies based on declarative data have suggested that the lockdown periods were associated with changes in psychoactive substance use but few relied on toxicological analyses.

Aims: We studied the impact of lockdowns on the pattern of routine care toxicological screening performed on patients hospitalized at the emergency ward (EW) and intensive care units (ICU) at the Grenoble University Hospital.

Variability of Tacrolimus Trough Concentration in Liver Transplant Patients: Which Role of Inflammation?

Tacrolimus presents high intra and inter-individual variability in its blood trough concentration (Cmin). Knowledge of the factors that are involved in tacrolimus Cmin variability is thus clinically important to prevent or limit it. Inflammation can affect the pharmacokinetic properties of drugs.

Homicidal poisoning series in a nursing home: retrospective toxicological investigations in bone marrow and hair.

Homicidal poisonings remain rare and can be difficult to detect, especially in the elderly or in medical settings. In this atypical poisoning series, a young nursing assistant purposely poisoned thirteen residents of a nursing home and killed ten of them. The medications used were a mix of psychotropic medications (cyamemazine, loxapine, tiapride, risperidone, and mirtazapine), under liquid formulation, which were inducing malaise and coma.

Combined Impact of Inflammation and Pharmacogenomic Variants on Voriconazole Trough Concentrations: A Meta-Analysis of Individual Data.

Few studies have simultaneously investigated the impact of inflammation and genetic polymorphisms of cytochromes P450 2C19 and 3A4 on voriconazole trough concentrations. We aimed to define the respective impact of inflammation and genetic polymorphisms on voriconazole exposure by performing individual data meta-analyses. A systematic literature review was conducted using PubMed to identify studies focusing on voriconazole therapeutic drug monitoring with data of both inflammation (assessed by C-reactive protein level) and the pharmacogenomics of cytochromes P450.

A simple and easy-to-perform liquid chromatography-mass spectrometry method for the quantification of tacrolimus and its metabolites in human whole blood. Application to the determination of metabolic ratios in kidney transplant patients.

Tacrolimus is the cornerstone of immunosuppressive therapy in solid organ transplantation and its blood concentrations are routinely monitored. Tacrolimus is extensively metabolized into metabolites that are supposed to be nephrotoxic. Yet, few analytical methods have been described to simultaneously quantify tacrolimus and its main metabolites.

Variability of rituximab and tocilizumab trough concentrations in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) are eligible for treatment with therapeutic monoclonal antibodies (mAbs) that target tumor necrosis factor α (TNFα), as well as others, such as rituximab (RTX) and tocilizumab (TCZ). Although pharmacokinetic variability and the link between concentration-clinical response of anti-TNFα mAbs have been well-described, little is known about RTX and TCZ. We aimed to evaluate the variability of RTX and TCZ serum concentrations in RA patients treated in second-line and the relationship between RTX/TCZ concentrations and the clinical response.