Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of BI 639667 in Healthy Male Subjects (Single-blind, Partially Randomised, Placebo-controlled Parallel Group Design)

The primary objective of this trial is to investigate the safety and tolerability of BI 639667 in healthy male subjects following oral administration of single rising doses.
Secondary objectives are the exploration of the pharmacokinetics (PK) including dose proportionality as well as investigation of linearity and pharmacodynamics (PD) of BI 639667 after single dosing and the assessment of the PK/PD relationship.

开始日期2014-07-01

申办/合作机构

Boehringer Ingelheim GmbH

100 项与 BI-639667 相关的临床结果

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100 项与 BI-639667 相关的转化医学

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100 项与 BI-639667 相关的专利（医药）

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项与 BI-639667 相关的文献（医药）

2022-08-09·Journal of Basic and Clinical Physiology and Pharmacology

Chemokine receptor antagonists with α₁-adrenergic receptor blocker activity

Article

作者: Enten, Garrett A. ; Gao, Xianlong ; DeSantis, Anthony J. ; Majetschak, Matthias

AbstractObjectivesChemokine receptor antagonists are being explored for their therapeutic potential in various disease processes. As the chemokine (C–C motif) receptor 2 (CCR2) antagonist RS504393 is known to compete with ligand binding to α1-adrenoceptors, we tested a panel of 10 CCR antagonists for interactions with α1-adrenoceptors to evaluate potential cardiovascular activities and side-effect profiles.MethodsThe PRESTO-Tango β-arrestin recruitment assay was utilized to test whether the CCR antagonists interfere with α1b-AR activation upon stimulation with phenylephrine. Pressure myography with isolated rat resistance arteries was employed to assess their effects on phenylephrine-induced vasoconstriction. The following antagonists were tested: CCR1–BX471, BX513, BI639667; CCR2–RS504393, INCB3284; CCR3–SB328437; and CCR4–AZD2098, and C021; CCR5–Maraviroc; CCR10-BI6901. The pan-α1-adrenoceptor antagonist prazosin was used as control.ResultsAmong the CCR antagonists tested, RS504393, BX513, and C021 inhibited phenylephrine-induced β-arrestin recruitment to α1b-adrenoceptor and phenylephrine-induced vasoconstriction. While RS504393 functioned as a competitive α1-adrenoceptor blocker, BX513 and C021 functioned as noncompetitive α1-adrenoceptor antagonists in both assay systems. Furthermore, RS504393, BX513, and C021 dose-dependently dilated arteries that were fully preconstricted with phenylephrine.ConclusionsOur data suggest that CCR antagonists should be screened for cross-reactivity with α1-adrenoceptors to exclude potential adverse cardiovascular effects when used as anti inflammatory drugs.

100 项与 BI-639667 相关的药物交易

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