Absorption, metabolism, and excretion of [ C]dersimelagon, an investigational oral selective melanocortin 1 receptor agonist, in preclinical species and healthy volunteers.

Dersimelagon (formerly MT-7117) is a novel, orally administered nonpeptide small molecule selective agonist for melanocortin 1 receptor currently being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis (dcSSc). Findings of studies evaluating the absorption, distribution, metabolism, and excretion (ADME) of dersimelagon following a single dose of [ C]dersimelagon in healthy adult volunteers (N = 6) who participated in phase 1, single-center, open-label, mass balance study (NCT03503266), and in preclinical animal models are presented. Rapid absorption and elimination were observed following oral administration of [ C]dersimelagon in clinical and nonclinical studies, with a mean T of 30 min in rats and 1.

Results from a first-in-human study of dersimelagon, an investigational oral selective MC1R agonist.

Purpose: To describe outcomes from the first-in-human study of dersimelagon, an investigational oral selective MC1R agonist, under development for the treatment of erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP).

Methods: In this double-blind, placebo-controlled phase 1 study, the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending oral doses of dersimelagon in healthy participants were evaluated.

Results: Dersimelagon was generally well tolerated in healthy participants, with the most common TEAEs being lentigo (52.

The Oral Bioavailability and Effect of Various Gastric Conditions on the Pharmacokinetics of Dersimelagon in Healthy Adult Volunteers.

Dersimelagon is a novel orally administered selective agonist for melanocortin receptor 1 being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis. In this open-label, multicenter, randomized, two-cohort, sequential crossover study, the relative oral bioavailability of two tablet formulations of dersimelagon was evaluated, and the effect of various gastric conditions (from a high-fat meal, a proton-pump inhibitor, and an acidic carbonated beverage) on the pharmacokinetics of dersimelagon were assessed in healthy participants (N = 50). Both tablet formulations demonstrated rapid absorption, and the 100-mg tablets showed a 97% relative oral bioavailability versus 50-mg tablets.

Toxicological evaluation of acyl glucuronides utilizing half-lives, peptide adducts, and immunostimulation assays.

Chemical reactivity of acyl glucuronides (AGs) is believed to be involved in the toxicity of carboxylic acid-containing drugs. Both direct and immune-mediated toxicity have been suggested as possible mechanisms of toxicity; however, it remains unclear. In the present study, we performed assays of half-lives, peptide adducts, and immunostimulation to evaluate the potential risk of AGs of 21 drugs and analyzed the relationship to the toxic category.

Interactions of organic anion transporters and organic cation transporters with mycotoxins.

Mycotoxins are secondary metabolites of moulds that which exert adverse effects in humans and animals. It is known that direct cellular toxicity is often associated with increased cellular accumulation of toxic compounds, and membrane transport may be the first fundamental stage in the development of the cytotoxicity. To elucidate the entry pathway for mycotoxins into cells, we have investigated the interactions of human and rat organic anion transporters (hOATs/rOats) and human organic cation transporters (hOCTs) with mycotoxins using cells stably expressing hOATs/rOats/hOCTs.

Substrate deacylation mechanisms of serine-beta-lactamases.

The substrate deacylation mechanisms of serine-beta-lactamases (classes A, C and D) were investigated by theoretical calculations. The deacylation of class A proceeds via four elementary reactions. The rate-determining process is the tetrahedral intermediate (TI) formation and the activation energy is 24.

[A study of the long-term continuation rate of respiratory rehabilitation in a day care service].

The purpose of this study is to report on the continuation rate of an outpatient pulmonary rehabilitation service for people with pulmonary disease. In Japan, Kaigo Hoken, the long-term care insurance system for the elderly, went into effect on April 1, 2000. Under this system, a special day care service was established in our hospital in order to continue outpatient rehabilitation for the elderly with pulmonary diseases.

[A case of allergic bronchopulmonary aspergillosis followed by diagnostic imaging for 27 years].

This patient was a 28-year-old man who had been treated with steroids for recurrent asthmatic attacks since around the age of 20. At one time the steroid therapy was discontinued and other treatments, including bronchodilator therapy and desensitization therapy, were substituted. At age 28, he first consulted our hospital due to the recurrence of attacks.