A phase 1 open label study to assess the human mass balance and metabolite profile of C-fosmanogepix, a novel Gwt-1 inhibitor in healthy male participants.

Unlabelled: Fosmanogepix [FMGX; active form manogepix (MGX)], a novel antifungal, is currently being studied for the treatment of invasive fungal diseases caused by spp., spp., and other rare molds.

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.

Atogepant and sumatriptan: no clinically relevant drug-drug interactions in a randomized, open-label, crossover trial.

To evaluate pharmacokinetic interactions of atogepant with sumatriptan, an open-label, randomized, crossover study was conducted. Thirty healthy adults received atogepant 60 mg, sumatriptan 100 mg, or coadministered drugs. Primary end point was geometric mean ratios (GMRs) and 90% CIs of interventions for area under the plasma concentration-time curve from time 0 to t (AUC) or infinity (AUC) and peak plasma concentration (C).

Pharmacokinetics and safety of ubrogepant when coadministered with calcitonin gene-related peptide-targeted monoclonal antibody migraine preventives in participants with migraine: A randomized phase 1b drug-drug interaction study.

Objective: To evaluate the impact of two calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies (mAbs), erenumab and galcanezumab, on the pharmacokinetic (PK) profile, safety, and tolerability of ubrogepant.

Background: People taking CGRP-targeted mAbs for migraine prevention sometimes take ubrogepant, an oral small-molecule CGRP receptor antagonist, for acute treatment of breakthrough migraine attacks.

Design: In this two-arm, multicenter, open-label, phase 1b trial, adults with migraine were randomized to arm 1 (ubrogepant ± erenumab) or arm 2 (ubrogepant ± galcanezumab).

Single-Dose Pharmacokinetics and Safety of Atogepant in Adults With Hepatic Impairment: Results From an Open-Label, Phase 1 Trial.

Atogepant is a selective oral calcitonin gene-related peptide receptor antagonist in development for migraine prevention. Here, we report the pharmacokinetics (PK) and safety of single-dose 60 mg atogepant in participants with severe, moderate, or mild hepatic impairment and matched participants with normal hepatic function from an open-label, parallel-group, single-dose phase 1 trial. Thirty-two participants aged 45 to 72 years were enrolled, which included 8 each with severe, moderate, mild, or no hepatic impairment.

Time course of efficacy of ubrogepant for the acute treatment of migraine: Clinical implications.

Background: The full utility of an acute treatment requires examination of the entire time course of effect during a migraine attack. Here the time course of effect of ubrogepant is evaluated.

Methods: ACHIEVE-I and -II were double-blind, single-attack, Phase 3 trials.

Similar pharmacokinetics of three dosing regimens comprising two oral delayed-release mesalamine formulations in healthy adult volunteers: Randomised, open-label, parallel-group study.

Aims: Mesalamine is the first-line therapy for treating mild-to-moderate ulcerative colitis. Multiple mesalamine formulations are available, with similar safety and efficacy profiles. Mesalamine is commonly administered as divided dosing, although once-daily dosing may provide benefits for patients.

Evaluation of the Pharmacokinetic Interaction of Ubrogepant Coadministered With Sumatriptan and of the Safety of Ubrogepant With Triptans.

Objective: To evaluate the potential for pharmacokinetic interaction and the safety and tolerability when ubrogepant and sumatriptan are coadministered in a Phase 1 study in healthy participants, and to inform the safety and tolerability of ubrogepant alone and in combination with triptans in Phase 3 trials in participants with migraine.

Background: Calcitonin gene-related peptide is a potent vasodilatory neurotransmitter believed to play a key role in the pathophysiology of migraine. Ubrogepant (UBRELVY™) is a potent and selective antagonist of the human calcitonin gene-related peptide receptor approved for the acute treatment of migraine.

Ubrogepant Is Not Associated With Clinically Meaningful Elevations of Alanine Aminotransferase in Healthy Adult Males.

Ubrogepant is a novel, oral calcitonin gene-related peptide (CGRP) receptor antagonist intended for the acute treatment of migraine attacks. Ubrogepant has a chemical structure distinct from previous small-molecule CGRP receptor antagonists that were associated with elevated serum alanine aminotransferase (ALT) in clinical trials. Here, we report overall and hepatic safety data from two placebo-controlled phase I trials of ubrogepant, spray-dried oral compressed tablet (SD-OCT) in healthy male volunteers.

Single Therapeutic and Supratherapeutic Doses of Ubrogepant Do Not Affect Cardiac Repolarization in Healthy Adults: Results From a Randomized Trial.

Ubrogepant is a novel, oral calcitonin gene-related peptide receptor antagonist currently under US Food and Drug Administration (FDA) review for the acute treatment of migraine attacks. This double-blind, four-period crossover study compared the cardiac repolarization effect of therapeutic (100 mg) and supratherapeutic (400 mg) ubrogepant doses vs. placebo in healthy adults.

Safety and tolerability of ubrogepant following intermittent, high-frequency dosing: Randomized, placebo-controlled trial in healthy adults.

Background: Ubrogepant is a novel, oral calcitonin gene-related peptide (CGRP) receptor antagonist in development for the acute treatment of migraine. This trial evaluated the safety and tolerability of ubrogepant, focusing on hepatic safety, when administered intermittently with high-frequency dosing to healthy participants.

Methods: In this phase 1, multicenter, double-blind, parallel-group trial, healthy adults (age 18-50 years) were randomized 1:1 to placebo or ubrogepant.

Bioavailability and swallowability of an age-appropriate, delayed-release mesalamine formulation in healthy volunteers.

Delayed-release mesalamine 400 mg capsules containing four 100 mg tablets have been developed for children with ulcerative colitis who have difficulty swallowing. Bioavailability of the mesalamine capsules was compared with existing mesalamine tablets in healthy adults, and the effect of food on bioavailability from mesalamine capsules was determined. Tablet swallowability in healthy children was evaluated.

Asenapine pharmacokinetics and tolerability in a pediatric population.

Purpose: This study aimed to characterize the pharmacokinetic (PK) properties, safety, and tolerability of asenapine, and to develop a population PK model in pediatric patients with schizophrenia, bipolar disorder, or other psychiatric disorders.

Methods: Two Phase I multiple ascending-dose studies were conducted to evaluate the PK, safety, and tolerability of sublingual asenapine in pediatric patients (age 10-17 years) with schizophrenia or bipolar I disorder. Patients received asenapine 1-10 mg twice daily for up to 12 days.

Rationale for nebivolol/valsartan combination for hypertension: review of preclinical and clinical data.

: To treat hypertension, combining two or more antihypertensive drugs from different classes is often necessary. β-Blockers and renin-angiotensin-aldosterone system inhibitors, when combined, have been deemed 'less effective' based on partially overlapping mechanisms of action and limited evidence. Recently, the single-pill combination (SPC) of nebivolol (Neb) 5 mg - a vasodilatory β1-selective antagonist/β3 agonist - and valsartan 80 mg, an angiotensin II receptor blocker, was US Food and Drug Administration-approved for hypertension.

A series of pharmacokinetic studies of ceftaroline fosamil in select populations: normal subjects, healthy elderly subjects, and subjects with renal impairment or end-stage renal disease requiring hemodialysis.

Ceftaroline fosamil is a parenteral cephalosporin indicated for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Ceftaroline, the active component of ceftaroline fosamil, exhibits broad-spectrum bactericidal activity against gram-positive organisms, including methicillin-resistant Staphylococcus aureus and Streptococcus pneumoniae, as well as common gram-negative pathogens. The objective of the studies presented herein was to establish the pharmacokinetic profile of ceftaroline in healthy subjects and special populations of interest, such as elderly subjects, subjects with renal impairment, or subjects with end-stage renal disease on intermittent hemodialysis.

Pharmacokinetic profile of dexloxiglumide.

Dexloxiglumide is a potent and selective cholecystokinin type 1 (CCK1) receptor antagonist currently under development in a variety of diseases affecting the gastrointestinal tract such as gastro-oesophageal reflux disease, irritable bowel syndrome (IBS), functional dyspepsia, constipation and gastric emptying disorders. In female patients with constipation-predominant IBS, clinical efficacy has been demonstrated following administration of dexloxiglumide 200 mg three times daily. Dexloxiglumide is rapidly and extensively absorbed after single oral administration in humans with an absolute bioavailability of 48%.

Effect of azole antifungals ketoconazole and fluconazole on the pharmacokinetics of dexloxiglumide.

Aims: Dexloxiglumide is a new CCK(1) receptor antagonist under investigation for treatment of functional gastrointestinal disorders and is metabolized by CYP3A4 and CYP2C9. The objectives of these two separate randomized, two-period, two-treatment crossover studies were to investigate the effects of steady-state ketoconazole, a model CYP3A4 inhibitor (Study 1), and steady-state fluconazole, a model CYP2C9 inhibitor (Study 2), on the pharmacokinetics of dexloxiglumide in healthy subjects.

Methods: Plasma samples were analysed for dexloxiglumide and its primary metabolites: O-demethyl dexloxiglumide (ODM; Study 1 and 2) and dexloxiglumide carboxylic acid (DCA; Study 2).

Effect of multiple-dose dexloxiglumide on the pharmacokinetics of oral contraceptives in healthy women.

This study was undertaken to evaluate the effect of dexloxiglumide, a selective cholecystokinin receptor antagonist, on the pharmacokinetics of a combination oral contraceptive (OC). A single-blind, placebo-controlled, 2-period crossover study was conducted in 24 healthy young female subjects who received Ortho Tri-Cyclen containing ethinyl estradiol (EE, 0.035 mg) and norgestimate (NE, 0.

Fibrinogen-coated droplets of olive oil for delivery of docetaxel to a fibrin(ogen)-rich ascites form of a murine mammary tumor.

Micronized droplets of olive oil loaded with docetaxel and coated with functional fibrinogen were administered intraperitoneally to mice bearing the fibrin(ogen)-rich ascites form of the TA3/St mammary tumor. When compared with docetaxel administered intraperitoneally as its commercial formulation (i.e.

Preparation, characterization, and preliminary application of fibrinogen-coated olive oil droplets for the targeted delivery of docetaxel to solid malignancies.

Micronized droplets of olive oil loaded with docetaxel (1.0 mg.ml(-1)) and coated with fibrinogen were prepared and then characterized for physicochemical and cytotoxic properties in vitro and anticancer activity in vivo.

Bioavailability, disposition, and dose-response effects of soy isoflavones when consumed by healthy women at physiologically typical dietary intakes.

The pharmacokinetics of isoflavones in 10 healthy women were determined from serum appearance/disappearance concentration profiles and urinary excretions after single-bolus ingestion of 10, 20 or 40 g of soy nuts delivering increasing amounts of the conjugated forms of daidzein (6.6, 13.2 and 26.