Mass Balance Recovery, Absorption, Metabolism, and Excretion of Elinzanetant in Healthy Human Volunteers and in vitro Biotransformation.

Background: Elinzanetant is a dual neurokinin-1,3 receptor antagonist in development for the treatment of menopausal vasomotor symptoms. The objectives of these studies were to characterize the mass balance and biotransformation of elinzanetant.

Methods: In the clinical evaluation, whole blood, plasma, urine, and feces were collected from healthy fasted male volunteers (n = 6) following a single dose of 120 mg [C]-elinzanetant oral suspension for analysis of total radioactivity and metabolite profiling.

The Effect of Hepatic Impairment on the Pharmacokinetics of Intravenously Administered Felcisetrag (TAK-954).

Felcisetrag (formerly known as TAK-954) is a selective serotonin receptor agonist under investigation for use in patients with postoperative gastrointestinal dysfunction. The safety, tolerability, and pharmacokinetics (PK) of intravenous (i.v.

Evaluation of the Pharmacokinetics of Felcisetrag (TAK-954), a 5-HT Receptor Agonist, in the Presence and Absence of Itraconazole, a Potent CYP3A4 Inhibitor.

The 5-hydroxytryptamine type-4 receptor agonist felcisetrag (TAK-954) is being investigated for improving gastrointestinal motility in postoperative gastrointestinal dysfunction. Polypharmacy often occurs in this setting, and as in vitro data indicate, felcisetrag is primarily metabolized by cytochrome P450 (CYP) 3A4, its CYP3A4-mediated drug-drug interaction potential requires consideration. This phase 1, fixed-sequence, open-label, crossover trial (ClinicalTrials.

Reduced sodium transport with nasal administration of the prostasin inhibitor camostat in subjects with cystic fibrosis.

Background: Prostasin, a trypsin-like serine protease, is a channel-activating protease and major regulator of epithelial sodium channel-mediated sodium absorption. Its direct inhibition by camostat represents a potential approach to inhibiting sodium transport in cystic fibrosis (CF).

Methods: To determine whether a topical formulation of camostat represents an efficacious and tolerable approach to reducing Na+ transport in the CF airway, we conducted a two-part randomized, double-blind, placebo-controlled, crossover, ascending single-dose study to evaluate the pharmacodynamics, safety, and pharmacokinetics of camostat administered through a nasal spray pump in subjects with CF.

Challenges in inhaled product development and opportunities for open innovation.

Dosimetry, safety and the efficacy of drugs in the lungs are critical factors in the development of inhaled medicines. This article considers the challenges in each of these areas with reference to current industry practices for developing inhaled products, and suggests collaborative scientific approaches to address these challenges. The portfolio of molecules requiring delivery by inhalation has expanded rapidly to include novel drugs for lung disease, combination therapies, biopharmaceuticals and candidates for systemic delivery via the lung.

Emerging therapies for respiratory diseases.

This Society for Medicines Research symposium, sponsored by UCB, was held on September 11, 2007, at the Wellcome Trust Conference Centre, Hinxton, Cambridge, United Kingdom. The meeting, organized by Ruth Lock, Steve Collingwood and Andrew Ratcliffe, reviewed current thinking in the area of airway drug delivery and the challenges and progress made in the discovery and development of novel medicines to treat respiratory diseases, such as chronic obstructive pulmonary disease, asthma, allergic rhinitis and cystic fibrosis.