Phase 1 pharmacokinetic and safety study of soticlestat in participants with mild or moderate hepatic impairment or normal hepatic function.

This phase 1, open-label, three-arm study (NCT05098054) compared the pharmacokinetics and safety of soticlestat (TAK-935) in participants with hepatic impairment. Participants aged ≥18 to <75 years had moderate (Child-Pugh B) or mild (Child-Pugh A) hepatic impairment or normal hepatic function (matched to hepatic-impaired participants by sex, age, and body mass index). Soticlestat was administered as a single oral 300 mg dose.

Comparative analysis of gut microbiome of mangrove brachyuran crabs revealed patterns of phylosymbiosis and codiversification.

The acquisition of microbial symbionts enables animals to rapidly adapt to and exploit novel ecological niches, thus significantly enhancing the evolutionary fitness and success of their hosts. However, the dynamics of host-microbe interactions and their evolutionary implications remain largely underexplored in marine invertebrates. Crabs of the family Sesarmidae (Crustacea: Brachyura) are dominant inhabitants of mangrove forests and are considered keystone species there.

Metagenomic analysis of gut microbiome illuminates the mechanisms and evolution of lignocellulose degradation in mangrove herbivorous crabs.

Background: Sesarmid crabs dominate mangrove habitats as the major primary consumers, which facilitates the trophic link and nutrient recycling in the ecosystem. Therefore, the adaptations and mechanisms of sesarmid crabs to herbivory are not only crucial to terrestrialization and its evolutionary success, but also to the healthy functioning of mangrove ecosystems. Although endogenous cellulase expressions were reported in crabs, it remains unknown if endogenous enzymes alone can complete the whole lignocellulolytic pathway, or if they also depend on the contribution from the intestinal microbiome.

Effects of Strong Inhibition of Cytochrome P450 3A and UDP glucuronosyltransferase 1A9 and Strong Induction of Cytochrome P450 3A on the Pharmacokinetics, Safety, and Tolerability of Soticlestat: Two Drug-Drug Interaction Studies in Healthy Volunteers.

Two open-label, phase 1 studies (NCT05064449, NCT05098041) investigated the effects of cytochrome P450 (CYP) 3A inhibition (via itraconazole), UDP glucuronosyltransferase (UGT) 1A9 inhibition (via mefenamic acid), and CYP3A induction (via rifampin) on the pharmacokinetics of soticlestat and its metabolites M-I and M3. In period 1 of both studies, participants received a single dose of soticlestat 300 mg. In period 2, participants received itraconazole on days 1-11 and soticlestat 300 mg on day 5 (itraconazole/mefenamic acid study; part 1); mefenamic acid on days 1-7 and soticlestat 300 mg on day 2 (itraconazole/mefenamic acid study; part 2); or rifampin on days 1-13 and soticlestat 300 mg on day 11 (rifampin study).

Investigation of the absolute bioavailability, mass balance, metabolism, and excretion of the cholesterol 24-hydroxylase inhibitor soticlestat in healthy volunteers.

Aims: Our aim was to determine the absolute bioavailability, mass balance, metabolism and excretion of soticlestat (TAK-935).

Methods: An open-label, two-period, single-site, phase 1 study was conducted in six healthy men. In Period 1, a single 300 mg dose of soticlestat was administered orally, followed by a 15-min intravenous infusion of [ C]soticlestat 50 μg (~1 μCi) 10 min later.

Integrating Regulatory Drug Label Information to Facilitate Evaluation of Adverse Events in Pharmacovigilance.

Background: Efficiency and accuracy for signal detection and evaluation activities are integral components of routine Pharmacovigilance (PV) practices. However, an Individual Case Safety Report (ICSR) may consist of a variety of confounders such as Concomitant Medications (CM), Past Medical History (PMH), and concurrent medical conditions that influence a safety officer's evaluation of a potential Adverse Event (AE). Limited pharmacovigilance systems are currently available as a tool designed to enhance the efficiency and accuracy of signal detection and management.

Melanoma in children and the use of sentinel lymph node biopsy.

Background: The rarity of pediatric melanoma prompted our review of sentinel lymph node biopsy (SLNB) and associated prognosis.

Methods: A chart review from 1989 to 2004 revealed 12 cases of cutaneous melanoma. Variables analyzed included demographics, site, histology, tumor characteristics, nodal status, and distant metastasis (TMN status), SLNB and/or therapeutic lymph node dissection (TLND), adjuvant treatment, disease-free survival, and overall survival.