Pharmacokinetics, Safety, and Tolerability of the α 2C -Adrenoreceptor Antagonist BAY 1193397 in Healthy Male Subjects.

Autor: Kapsa S; Clinical Pharmacokinetics, BAYER AG, Wuppertal, Germany., Thuss U; Bioanalytics, BAYER AG, Wuppertal, Germany., Boxnick S; CRS Clinical Research Services, Wuppertal GmbH, Wuppertal, Germany., Schaumann F; CRS Clinical Research Services, Wuppertal GmbH, Wuppertal, Germany., Schultz A; CRS Clinical Research Services, Mannheim GmbH, Mannheim, Germany., Unger S; Research and Early Development Statistics, BAYER AG, Wuppertal, Germany., Otto C; Clinical Experimentation Cardiovascular, BAYER AG, Wuppertal, Germany.
Jazyk: angličtina
Zdroj: Clinical pharmacology in drug development [Clin Pharmacol Drug Dev] 2022 Mar; Vol. 11 (3), pp. 296-308. Date of Electronic Publication: 2021 Aug 31.
DOI: 10.1002/cpdd.1018
Abstrakt: The α 2C -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). BAY 1193397 was rapidly absorbed in the fasted state, peak concentrations were reached between 0.6 and 2 hours. The mean terminal half-life was in the range of 17 to 20 hours. Area under the plasma concentration-time curve and maximum concentration appeared to be dose proportional, with a negligible food effect. There were no high-accumulation effects of BAY 1193397 after repeated dosing. BAY 1193397 was safe and well tolerated. At supratherapeutic plasma concentrations, there were slight transient increases in norepinephrine levels, heart rate, and blood pressure that were more pronounced after a single dose compared to steady state and appeared to be maximum concentration dependent. The results of the presented studies support the conduct of subsequent clinical trials with BAY 1193397 in patients with diabetes and compromised microcirculation.
(© 2021, The American College of Clinical Pharmacology.)
Databáze: MEDLINE
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