Phase 1 drug-drug interaction study to assess the effect of CYP3A4 inhibition and pan-CYP induction on the pharmacokinetics and safety of fosmanogepix in healthy participants.

Unlabelled: Immunocompromised patients are susceptible to fungal infections, and drug-drug interactions with antifungals may occur due to concomitant medications. Fosmanogepix [FMGX; active moiety manogepix (MGX)] targets glycosylphosphatidylinositol-anchored mannoprotein synthesis and maturation, essential for fungal virulence. This phase 1, fixed-sequence study in healthy participants evaluated the effect of strong CYP3A4 inhibitor itraconazole [Cohort 1 ( = 18); FMGX 500 mg intravenous (IV) twice a day (BID )+ itraconazole 200 mg oral once a day (QD)] and pan-CYP inducer rifampin [Cohort 2 ( = 18); FMGX 1,000 mg IV BID + rifampin 600 mg oral QD] on the pharmacokinetics of FMGX and MGX.

Pharmacokinetics, safety, and tolerability of fosmanogepix IV to oral switch and multiple IV doses in healthy participants.

Fosmanogepix [FMGX, APX001; active form: manogepix (MGX), APX001A] is a first-in-class, intravenous (IV)/oral antifungal currently being evaluated for invasive fungal disease treatment. Data from two phase 1, placebo-controlled studies [IV-oral switch (study 1) and multiple IV doses (study 2)] evaluating FMGX tolerability, and pharmacokinetics (PK) are presented. Healthy adults (study 1: 18-65 years; study 2: 18-55 years) were eligible (randomized 3:1 to FMGX: placebo).

Safety and Pharmacokinetics of Intravenous and Oral Fosmanogepix, a First-in-Class Antifungal Agent, in Healthy Volunteers.

Fosmanogepix (FMGX, APX001), a first-in-class, intravenous (i.v.) and oral (p.

EDP-297: A novel, farnesoid X receptor agonist-Results of a phase I study in healthy subjects.

EDP-297 is a farnesoid X receptor agonist under development for treating nonalcoholic steatohepatitis. The pharmacokinetic (PK), pharmacodynamic (PD), food effect, and safety were evaluated in a single ascending dose (SAD) and multiple ascending dose (MAD) phase I study. Healthy subjects received single EDP-297 doses of 20-600 μg or once daily doses of 5-90 μg for 14 days.

Comparison of the injection-site experience of the starting doses with semaglutide and dulaglutide: A randomized, double-blind trial in healthy subjects.

This double-blind, randomized, single-site, crossover trial compared the injection-site experience with the starting doses of semaglutide and dulaglutide. Healthy subjects (aged 18-75 years; body mass index ≥ 25 kg/m ; n = 104) were randomized 1:1, using a pregenerated list, to semaglutide 0.25 mg as the first injection and dulaglutide 0.

Metabolism and Excretion of Intravenous, Radio-Labeled Amisulpride in Healthy, Adult Volunteers.

Purpose: Intravenous amisulpride, a dopamine D/D antagonist, has recently been shown in trials to be an effective antiemetic at low doses. This study was conducted to investigate the metabolism and elimination of a single dose of intravenous C-labeled amisulpride in healthy, adult volunteers.

Patients And Methods: Six healthy male volunteers aged 18-65 years were given a single 10 mg dose of C-labeled amisulpride containing not more than 1.

Safety, tolerability, pharmacokinetics and pharmacodynamics of GSK2239633, a CC-chemokine receptor 4 antagonist, in healthy male subjects: results from an open-label and from a randomised study.

Background: The CC-chemokine receptor 4 (CCR4) is thought potentially to play a critical role in asthma pathogenesis due to its ability to recruit type 2 T-helper lymphocytes to the inflamed airways. Therefore, CCR4 provides an excellent target for anti-inflammatory therapy.

Methods: The safety, tolerability, pharmacokinetics and pharmacodynamics of the CCR4 antagonist GSK2239633, N-(3-((3-(5-chlorothiophene-2-sulfonamido)-4-methoxy-1H-indazol-1-yl)methyl)benzyl)-2-hydroxy-2-methylpropanamide, were examined in healthy males.

Absorption, metabolism and excretion of darexaban (YM150), a new direct factor Xa inhibitor in humans.

1. The absorption, metabolism and excretion of darexaban (YM150), a novel oral direct factor Xa inhibitor, were investigated after a single oral administration of [(14)C]darexaban maleate at a dose of 60 mg in healthy male human subjects. 2.

Pharmacokinetic properties of mirabegron, a β3-adrenoceptor agonist: results from two phase I, randomized, multiple-dose studies in healthy young and elderly men and women.

Background: Mirabegron (YM178) is a β(3)-adrenoceptor agonist for the treatment of overactive bladder (OAB). As part of the clinical development program for mirabegron, 2 human volunteer studies were performed to derive detailed data on the multiple-dose pharmacokinetic (PK) properties of mirabegron.

Objective: Two randomized Phase I studies were conducted to evaluate the PK properties of mirabegron, including metabolic profile and effects of age and sex, following multiple oral doses in healthy subjects.

Single dose pharmacokinetics and absolute bioavailability of mirabegron, a β₃-adrenoceptor agonist for treatment of overactive bladder.

Background And Objectives: Mirabegron is a potent and selective β3-adrenoceptor agonist in development for treatment of overactive bladder.

Methods: Mirabegron pharmacokinetics after single intravenous (i.v.

Sugammadex is cleared rapidly and primarily unchanged via renal excretion.

Sugammadex is a modified γ-cyclodextrin which rapidly reverses rocuronium-and vecuronium-induced neuromuscular blockade. Previous studies suggest that sugammadex is mostly excreted unchanged via the kidneys. This single-center, open-label, non-randomized study used (14)C-labeled sugammadex to further investigate the excretion, metabolic and pharmacokinetic (PK) profiles of sugammadex in six healthy male volunteers.

Pharmacokinetic characterization of the novel pulmonary delivery excipient fumaryl diketopiperazine.

Background: Technosphere® [Bis-3,6(4-fumarylaminobutyl)-2,5-diketopiperazine (FDKP)] microparticles, the integral component of the Technosphere inhalation system, deliver drugs to the deep lung and have been used to administer insulin and glucagon-like peptide-1 via inhalation in clinical studies. Three studies were conducted to characterize FDKP pharmacokinetics, including assessments in subjects with diabetic nephropathy (DNP), in subjects with chronic liver disease (CLD), and in healthy subjects.

Methods: An open-label, nonrandomized, two-period, fixed-sequence crossover absorption, distribution, metabolism, and excretion (ADME) study was conducted in six healthy nonsmoking men who received single intravenous and oral doses of [(14)C]FDKP solution, with serial sampling of blood, urine, feces, and expired air.

Hypertensive crisis-induced electrocardiographic changes: a case series.

Introduction: Myocardial injury is one of the most notorious complications of a hypertensive crisis. Key electrocardiograph signs used to detect cardiac injury such as ST segment changes and cardiac arrhythmias usually indicate acute ongoing end-organ damage. Lack of early signs to predict end-organ damage might lead to a delay in the initiation of therapy and selection of the incorrect therapeutic strategy.

Pharmacokinetics of [14C]ciclesonide after oral and intravenous administration to healthy subjects.

Background: Ciclesonide is a novel inhaled corticosteroid developed for the treatment of asthma.

Objective: To investigate the extent of oral absorption and bioavailability of ciclesonide referenced to an intravenous infusion. This information provides an estimate for the contribution of the swallowed fraction to systemic exposure to ciclesonide after oral inhalation.