PMID- 38344891
OWN - NLM
STAT- MEDLINE
DCOM- 20240214
LR  - 20240417
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 17
IP  - 2
DP  - 2024 Feb
TI  - Utilizing venous occlusion plethysmography to assess vascular effects: A study 
      with buloxibutid, an angiotensin II type 2 receptor agonist.
PG  - e13735
LID - 10.1111/cts.13735 [doi]
LID - e13735
AB  - Buloxibutid (also known as C21) is a potent and selective angiotensin II type 2 
      receptor (AT2R) agonist, in development for oral treatment of fibrotic lung 
      disease. This phase I, open-label, pharmacodynamic study investigated vascular 
      effects of buloxibutid in five healthy male volunteers. Subjects were 
      administered intra-arterial infusions of buloxibutid for 5 min in ascending doses 
      of 3, 10, 30, 100, and 200 mug/min, infused sequentially in the forearm. Infusions 
      of sodium nitroprusside (SNP) solution in doses of 0.8-3.2 mug/min were 
      administered as a positive control. Forearm blood flow (FBF) was measured by 
      venous occlusion plethysmography. Safety and tolerability of intra-arterial 
      administrations of buloxibutid were evaluated. Following infusion of buloxibutid 
      in doses of 3-200 mug/min, the range of increase in FBF was 27.8%, 17.2%, 37.0%, 
      28.5%, and 60.5%, compared to the respective baseline. The largest increase was 
      observed in the highest dose group. Infusions of SNP as a positive control, 
      increased FBF 230-320% compared to baseline. Three adverse events (AEs) of mild 
      intensity, not related to buloxibutid or SNP, were reported for two subjects. Two 
      of these AEs were related to study procedures. There were no clinically relevant 
      changes in arterial blood pressure during the study period. Intra-arterial 
      infusion of buloxibutid in low, ascending doses increased FBF, indicating that 
      buloxibutid may be effective in conditions associated with endothelial 
      dysfunction. Venous occlusion plethysmography was found to be a useful method to 
      explore pharmacodynamic vascular effects of novel AT2R agonists, while avoiding 
      systemic adverse effects.
CI  - (c) 2024 The Authors. Clinical and Translational Science published by Wiley 
      Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Rein-Hedin, Erik
AU  - Rein-Hedin E
AUID- ORCID: 0000-0002-9462-1785
AD  - CTC Clinical Trial Consultants AB, Uppsala, Sweden.
AD  - Department of Surgical Sciences, Plastic Surgery, Uppsala University, Uppsala, 
      Sweden.
FAU - Sjoberg, Folke
AU  - Sjoberg F
AUID- ORCID: 0000-0002-5903-2918
AD  - CTC Clinical Trial Consultants AB, Uppsala, Sweden.
AD  - Department of Biomedical and Clinical Sciences, Linkoping University, Linkoping, 
      Sweden.
FAU - Ganslandt, Cecilia
AU  - Ganslandt C
AD  - Vicore Pharma AB, Stockholm, Sweden.
FAU - Skoog, Johan
AU  - Skoog J
AUID- ORCID: 0000-0002-4507-8392
AD  - Department of Clinical Physiology and Department of Health, Medicine and Caring 
      Sciences, Linkoping University, Linkoping, Sweden.
FAU - Zachrisson, Helene
AU  - Zachrisson H
AUID- ORCID: 0000-0001-6536-468X
AD  - Department of Clinical Physiology and Department of Health, Medicine and Caring 
      Sciences, Linkoping University, Linkoping, Sweden.
FAU - Bengtsson, Thomas
AU  - Bengtsson T
AD  - StatMind AB, Lund, Sweden.
FAU - Dalsgaard, Carl-Johan
AU  - Dalsgaard CJ
AD  - Vicore Pharma AB, Stockholm, Sweden.
LA  - eng
SI  - ClinicalTrials.gov/NCT05277922
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 169D1260KM (Nitroprusside)
SB  - IM
MH  - Humans
MH  - Male
MH  - *Receptor, Angiotensin, Type 2
MH  - Nitroprusside/adverse effects
MH  - *Plethysmography/methods
MH  - Forearm/blood supply
MH  - Regional Blood Flow
MH  - Vasodilation
PMC - PMC10859786
COIS- C.G. and CJ.D. are employees of, and hold shares/share options in, Vicore Pharma 
      AB. T.B. declares consultancy fees from Vicore Pharma AB. All other authors 
      declared no competing interests for this work.
EDAT- 2024/02/12 15:44
MHDA- 2024/02/12 15:45
PMCR- 2024/02/12
CRDT- 2024/02/12 05:34
PHST- 2023/11/22 00:00 [revised]
PHST- 2023/09/22 00:00 [received]
PHST- 2024/01/21 00:00 [accepted]
PHST- 2024/02/12 15:45 [medline]
PHST- 2024/02/12 15:44 [pubmed]
PHST- 2024/02/12 05:34 [entrez]
PHST- 2024/02/12 00:00 [pmc-release]
AID - CTS13735 [pii]
AID - 10.1111/cts.13735 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2024 Feb;17(2):e13735. doi: 10.1111/cts.13735.