Doppler ultrasound to assess the pharmacodynamic effects of splanchnic vasoactive compounds

Aims In search of noninvasive biomarkers to assess the pharmacodynamic effects of portal pressure‐lowering drugs, the reproducibility of flow measurements in the superior mesenteric artery was evaluated using Doppler ultrasound. Methods A reproducibility study was conducted in 15 healthy male volunt...

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Veröffentlicht in:British journal of clinical pharmacology 2022-02, Vol.88 (4), p.1785-1794
Hauptverfasser: Marynissen, Heleen, Lodeweyckx, Thomas, Bielen, Didier, Hoon, Jan
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Sprache:eng
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Zusammenfassung:Aims In search of noninvasive biomarkers to assess the pharmacodynamic effects of portal pressure‐lowering drugs, the reproducibility of flow measurements in the superior mesenteric artery was evaluated using Doppler ultrasound. Methods A reproducibility study was conducted in 15 healthy male volunteers (18–50 y). Eight ultrasound measurements were performed for each subject: 2 observers each conducted 2 measurements during 2 separate visits. The following flow parameters were captured: peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI), volume flow (VF) and vessel diameter. Reproducibility was assessed by the intraclass correlation coefficient. Results Results are presented as intraclass correlation coefficient [95% confidence interval]. The flow parameters PSV, EDV, PI and VF correlated excellently within observer during visit 1 (0.888 [0.748–0.953], 0.910 [0.793–0.962], 0.844 [0.656–0.933] and 0.916 [0.857–0.951], respectively) and visit 2 (0.925 [0.829–0.968], 0.942 [0.863–0.976], 0.883 [0.719–0.954] and 0.915 [0.855–0.951], respectively). Measurements conducted during 2 separate visits by 1 observer correlated well to excellently for PSV, EDV, PI and VF (0.756 [0.552–0.875], 0.836 [0.694–0.916], 0.807 [0.631–0.904] and 0.839 [0.783–0.882], respectively). Measurements conducted by 2 distinct observers correlated well to excellently for PSV, EDV and VF during visit 1 (0.813 [0.584–0.922], 0.884 [0.597–0.945] and 0.786 [0.575–0.899], respectively) and visit 2 (0.779 [0.498–0.912], 0.861 [0.672–0.945], 0.810 [0.553–0.926], respectively). Vessel diameter measurements were poorly reproducible. Conclusion Doppler ultrasound is a reproducible method for flow measurements in the superior mesenteric artery in a standardized group of healthy volunteers. Therefore, it is a promising technique to assess pharmacodynamic effects of splanchnic vasoactive compounds in early clinical drug development.
ISSN:0306-5251
1365-2125
DOI:10.1111/bcp.15095