Activity

subjects and patients. None of the covariates evaluated have a clinically relevant impact on the pharmacokinetics of vixotrigine.Rhizosphere microbiome is one of the main sources of plant protection against drought. Beneficial symbiotic microorganisms, such as ectomycorrhizal fungi (ECMF) and mycorrhiza helper bacteria (MHB), interact with each other for increasing or maintaining host plant fitness. This mutual support benefits all three partners and comprises a natural system for drought acclimation in plants. Cork oak (Quercus suber L.) tolerance to drought scenarios is widely known, but adaptation to climate changes has been a challenge for forest sustainability protection. In this work, ECMF and MHB communities from cork oak forests were cross-linked and correlated with climates. Cenococcum, Russula and Tuber were the most abundant ECMF capable of interacting with MHB (ECMF~MHB) genera in cork oak stands, while Bacillus, Burkholderia and Streptomyces were the most conspicuous MHB. Integrating all microbial data, two consortia Lactarius/Bacillaceae and Russula/Burkholderaceae have singled out but revealed a negative interaction with each other. Russula/Burkholderaceae might have an important role for cork oak forest sustainability in arid environments, which will be complemented by the lower drought adaptation of competitive Lactarius/Bacillaceae. These microbial consortia could play an essential role on cork oak forest resilience to upcoming climatic changes.

The first oral glucagon-like peptide-1 receptor agonist (GLP-1RA) comprises semaglutide co-formulated with the absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). Oral semaglutide may alter the pharmacokinetics of co-administered drugs via effects of semaglutide or SNAC. Two separate one-sequence crossover trials investigated the effects of oral semaglutide and SNAC on the pharmacokinetics of ethinylestradiol, levonorgestrel, furosemide and rosuvastatin.

Healthy, postmenopausal women (n = 25) received once-daily combined ethinylestradiol and levonorgestrel (Trial 1) and healthy male and female subjects (n = 41) received single doses of furosemide and rosuvastatin (Trial 2), either alone, with SNAC alone or with oral semaglutide. Lack of drug-drug interaction was concluded if 90% confidence intervals (CIs) for the ratio of area under the plasma concentration-time curve (AUC) or maximum concentration (C

), with/without oral semaglutide, were within a pre-specified interval (0.80-1.25).

The AUC values of ethinylestradiol and levonorgestrel were not affected by oral semaglutide co-administration (estimated ratios [90% CI] 1.06 [1.01-1.10] and 1.06 [0.97-1.17], respectively); C

was not affected. BAY 87-2243 in vivo The no-effect criterion was not met for furosemide or rosuvastatin for the AUC (1.28 [1.16-1.42] and 1.41 [1.24-1.60], respectively) or C

. SNAC alone did not affect the AUC or C

of ethinylestradiol, levonorgestrel or rosuvastatin; the C

of furosemide was slightly decreased. Adverse events were similar to those previously observed for GLP-1RAs (both trials).

Co-administration with oral semaglutide did not affect the pharmacokinetics of ethinylestradiol or levonorgestrel. There was a small increase in exposure of furosemide and rosuvastatin; however, these increases are not expected to be of clinical relevance.

NCT02845219 and NCT03010475.

NCT02845219 and NCT03010475.

The objective of this study was to assess the pharmacokinetic and pharmacodynamic profiles and safety of edoxaban in patients with nonvalvular atrial fibrillation (NVAF) who were hospitalized with acute heart failure (AHF).

The trough plasma concentrations of edoxaban, and the coagulation biomarkers prothrombin fragments 1 and 2 (F1+2) and D-dimer, were determined. Twenty-six patients received edoxaban 60 mg (30 mg when dose adjustment was required) and blood samples were collected immediately before oral edoxaban administration for 7 consecutive days after hospitalization and on the day of discharge.

The mean observation period was 13 (range 7-46) days. Trough plasma concentrations of edoxaban were constant from day 2 onwards. On day 1, the variation was greater owing to the differing intervals between the last edoxaban dose and day 1 blood collection. Trough plasma concentrations were higher in patients with reduced creatinine clearance (≤ 50 mL/min). Median values for F1+2 and D-dimer remained within normal ranges throughout the study. There were no drug discontinuations, and no serious adverse events were reported.

This is the first study of edoxaban pharmacokinetics and pharmacodynamics in patients with NVAF and AHF, and shows that the pharmacokinetic and pharmacodynamic profiles of edoxaban were constant during hospitalization. Thus, even in patients with NVAF and AHF, edoxaban anticoagulation therapy with guided dose adjustment is considered to be a safe and appropriate intervention. In particular, patients with reduced creatinine clearance should adhere to dose adjustment criteria.

jRCTs031190006 (Japan Registry of Clinical Trials), 5 April, 2019 retrospectively registered.

jRCTs031190006 (Japan Registry of Clinical Trials), 5 April, 2019 retrospectively registered.Remdesivir (RDV, Veklury®) is a once-daily, nucleoside ribonucleic acid polymerase inhibitor of severe acute respiratory syndrome coronavirus 2 replication. Remdesivir has been granted approvals in several countries for use in adults and children hospitalized with severe coronavirus disease 2019 (COVID-19). Inside the cell, remdesivir undergoes metabolic activation to form the intracellular active triphosphate metabolite, GS-443902 (detected in peripheral blood mononuclear cells), and ultimately, the renally eliminated plasma metabolite GS-441524. This review discusses the pre-clinical pharmacology of RDV, clinical pharmacokinetics, pharmacodynamics/concentration-QT analysis, rationale for dose selection for treatment of patients with COVID-19, and drug-drug interaction potential based on available in vitro and clinical data in healthy volunteers. Following single-dose intravenous administration over 2 h of an RDV solution formulation across the dose range of 3-225 mg in healthy participants, RDV and its metabolites (GS-704277and GS-441524) exhibit linear pharmacokinetics.