Gadolinium Presence in Rat Skin: Assessment of Histopathologic Changes Associated with Small Fiber Neuropathy.

Background The presence of gadolinium traces in the skin after administration of gadolinium-based contrast agents (GBCAs) raised safety concerns regarding a potential association with small fiber neuropathy (SFN). Purpose To investigate signs of SFN in rat foot pads by quantification of the intraepidermal nerve fiber density (IENFD) after multiple GBCA administrations and to evaluate gadolinium concentration, chemical species, and clearance. Materials and Methods Fifty rats received eight intravenous injections of either gadodiamide, gadobutrol, gadoterate, gadoteridol (8 × 0.

First-in-human study of eliapixant (BAY 1817080), a highly selective P2X3 receptor antagonist: Tolerability, safety and pharmacokinetics.

Aims: Neuronal hypersensitisation due to adenosine triphosphate-dependent P2X3 receptor signalling plays a significant role in several disorders including chronic cough and endometriosis. This first-in-human study of eliapixant (BAY 1817080) investigated the tolerability, safety and pharmacokinetics (PK) of single doses of eliapixant, including the effect of food and coadministration with a CYP3A inhibitor on eliapixant relative bioavailability.

Methods: In this randomised, double-blind phase I study (NCT02817100), 88 healthy male subjects received single ascending doses of immediate-release eliapixant (10-800 mg) tablets or placebo under fasted conditions, with food (low-fat continental or high-fat American breakfast) or with itraconazole (fasted state).

Pharmacokinetics, Safety, and Tolerability of the α -Adrenoreceptor Antagonist BAY 1193397 in Healthy Male Subjects.

The α -adrenoreceptor antagonist BAY 1193397 is in development for the oral treatment of diabetic foot ulcers. Safety, tolerability, and pharmacokinetics of BAY 1193397 were investigated in 3 randomized, single-center phase 1 studies in healthy male subjects: a first-in-human study (single oral doses of 0.5-50 mg), a relative bioavailability and food effect study (single doses of 1 and 10 mg), and a multiple-dose escalation study (using 2 and 5 mg twice daily and 10 and 20 mg once daily for 9 consecutive days).

Absorption, distribution, metabolism and excretion of molidustat in healthy participants.

The absorption, distribution, metabolism and excretion of molidustat were investigated in healthy male participants. In study 1, a mass balance study, radiolabelled molidustat 25 mg (3.57 MBq) was administered as an oral solution (n = 4).

Rogaratinib: A potent and selective pan-FGFR inhibitor with broad antitumor activity in FGFR-overexpressing preclinical cancer models.

Aberrant activation in fibroblast growth factor signaling has been implicated in the development of various cancers, including squamous cell lung cancer, squamous cell head and neck carcinoma, colorectal and bladder cancer. Thus, fibroblast growth factor receptors (FGFRs) present promising targets for novel cancer therapeutics. Here, we evaluated the activity of a novel pan-FGFR inhibitor, rogaratinib, in biochemical, cellular and in vivo efficacy studies in a variety of preclinical cancer models.