Tablets or oral suspension for posaconazole in lung transplant recipients? Consequences for trough concentrations of tacrolimus and everolimus.

Aims: A new formulation of posaconazole (PCZ), delayed-release tablets (PCZ-tab), increases PCZ bioavailability and plasma trough concentrations (C ) over those achieved with an oral suspension (PCZ-susp). PCZ is an inhibitor of cytochrome P450 3A4 and P-glycoprotein. We therefore investigated the impact of PCZ-tab treatment on blood C and doses of tacrolimus (TAC) and everolimus (EVR).

Refining the therapeutic range of posaconazole and isavuconazole for efficient therapeutic drug monitoring using a bioassay approach.

Therapeutic drug monitoring (TDM) of antifungal triazole was recommended, except for isavuconazole (ISA) whose target trough concentrations (C ) need to be specified. Concerning posaconazole (POS), tablet formulation results in higher exposure but no upper C threshold has been yet proposed. We aimed to investigate the pharmacokinetic-pharmacodynamic relationship of POS and ISA, using a bioassay approach as surrogate marker of antifungal activity, in order to refine the therapeutic C of both antifungals.

Treatment by Posaconazole Tablets, Compared to Posaconazole Suspension, Does Not Reduce Variability of Posaconazole Trough Concentrations.

The delayed-release tablet formulation of posaconazole (POS-tab) results in higher plasma POS trough concentrations (C) than the oral suspension (POS-susp), which raises the question of the utility of therapeutic drug monitoring (TDM). We aimed to compare the variability of the POS C for the two formulations and identify determinants of the POS-tab C and its variability. Demographic, biological, and clinical data from 77 allogeneic hematopoietic stem cell transplant patients (874 C) treated with POS-tab ( = 41), POS-susp ( = 29), or both ( = 7) from January 2015 to December 2016 were collected retrospectively.

Inflammation is a potential risk factor of voriconazole overdose in hematological patients.

Voriconazole (VRC) overdoses are frequent and expose patients at high risk of adverse effects. This case-control study performed in hematological patients who benefited from VRC therapeutic drug monitoring from January 2012 to December 2015 aimed to identify risk factors of VRC overdose. Pharmacogenetic, biological, and demographic parameters at the time of VRC trough concentration (C ) were retrospectively collected from medical records.

Pharmacogenetics may influence the impact of inflammation on voriconazole trough concentrations.

How pharmacogenetics modulates the inhibitory effects of inflammation on voriconazole trough concentration (Cmin) remains unknown. In 29 recipients of allogeneic hematopoietic stem cell transplantation retrospectively studied, both a genetic score (which aggregated CYP2C19 and CYP3A genotypes) and inflammation significantly influenced voriconazole Cmin (n = 260). A trend toward (p = 0.

Alterations to mitochondrial fatty-acid use in skeletal muscle after chronic exposure to hypoxia depend on metabolic phenotype.

We investigated the effects of chronic hypoxia on the maximal use of and sensitivity of mitochondria to different substrates in rat slow-oxidative (soleus, SOL) and fast-glycolytic (extensor digitorum longus, EDL) muscles. We studied mitochondrial respiration in situ in permeabilized myofibers, using pyruvate, octanoate, palmitoyl-carnitine (PC), or palmitoyl-coenzyme A (PCoA). The hypophagia induced by hypoxia may also alter metabolism.

Infliximab quantitation in human plasma by liquid chromatography-tandem mass spectrometry: towards a standardization of the methods?

Infliximab (IFX) is a chimeric monoclonal antibody targeting tumor necrosis factor-alpha. It is currently approved for the treatment of certain rheumatic diseases or inflammatory bowel diseases. Clinical studies have suggested that monitoring IFX concentrations could improve treatment response.

Contribution of a Simple Bioassay in Effective Therapeutic Drug Monitoring of Posaconazole and Voriconazole.

Background: With the constantly growing incidence of invasive fungal infections, any failure of antifungal treatment is worrying. Azole antifungals present high variability of their plasma trough concentrations (Cmin), justifying their therapeutic drug monitoring (TDM). The authors aimed to develop a simple bioassay to determine the in vitro growth inhibition diameter (ID) and to correlate this ID with Cmin in patients treated with voriconazole or posaconazole.

Low Cardiorespiratory Fitness is Partially Linked to Ventilatory Factors in Obese Adolescents.

Aim: To examine the role of ventilatory constraint on cardiorespiratory fitness in obese adolescents.

Methods: Thirty obese adolescents performed a maximal incremental cycling exercise and were divided into 2 groups based on maximal oxygen uptake (VO2peak): those presenting low (L; n = 15; VO2peak: 72.9 ± 8.

Variability of voriconazole plasma concentrations after allogeneic hematopoietic stem cell transplantation: impact of cytochrome p450 polymorphisms and comedications on initial and subsequent trough levels.

Voriconazole (VRC) plasma trough concentrations (Cmin) are highly variable, and this could affect treatment efficacy and safety in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). We aimed to describe the intra- and interindividual variation of VRC Cmin throughout the course of VRC therapy and to identify the determinants of this variation. Clinical data, medications, and VRC Cmin (n = 308) of 33 AHSCT patients were retrospectively collected.

Simultaneous quantitation of azole antifungals, antibiotics, imatinib, and raltegravir in human plasma by two-dimensional high-performance liquid chromatography-tandem mass spectrometry.

High-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a standard analytical technique for therapeutic drug monitoring (TDM). A rapid LC-MS/MS method was developed for simultaneous quantitation of 3 antifungals and one active metabolite (posaconazole, voriconazole, itraconazole, and hydroxy-itraconazole), 5 antibiotics (daptomycin, ciprofloxacin, oxacillin, levofloxacin, and rifampicin), an antineoplastic agent (imatinib), and an antiretroviral (raltegravir) in human plasma. Protein precipitation of 10 μL of plasma with acetonitrile was used as a single-extraction procedure.

Effect of chronic intermittent hypoxia on exercise adaptations in healthy subjects.

Reduced exercise tolerance has been reported in obstructive sleep apnea syndrome (OSAS) patients, although the associated hypertension, obesity and/or metabolic disorder may underlie this reduction. Therefore, we evaluated the effects of chronic intermittent hypoxia (CIH) in 12 healthy subjects on exercise capacity, cardio-respiratory responses, and substrate oxidation during maximal and sub-maximal exercise. Subjects were exposed to 30 cycles of hypoxia-reoxygenation per hour for 14 nights.