Berthezène Y, Mühler A, Lang P, Shames D M, Clément O, Rosenau W, Kuwatsuru R, Brasch R C
Department of Radiology, University of California, San Francisco 94143-0628.
J Magn Reson Imaging. 1993 Jan-Feb;3(1):125-30. doi: 10.1002/jmri.1880030121.
This study evaluated the pharmacokinetics and potential toxicity of inhaled aerosolized gadopentetate dimeglumine. The pharmacokinetics were evaluated with in vitro relaxometry of the lungs, blood, urine, and liver before and for up to 36 hours after a 5-minute inhalation of aerosolized gadopentetate dimeglumine (0.25 mol/L). For assessment of potential toxicity, hemodynamic variables were monitored during and for 10 minutes after inhalation. Extravascular lung water was measured before and after exposure. Finally, the potential for tissue damage was evaluated histologically. Pulmonary clearance of aerosolized gadopentetate dimeglumine was monoexponential with a half-time of 2.16 hours. Aerosolized gadopentetate dimeglumine was excreted through the kidneys, as shown by the decrease in urinary T1. Renal elimination was completed by 30 hours. No acute hemodynamic effect, histologic change, or induction of edema was demonstrated. This study shows that inhalation of aerosolized gadopentetate dimeglumine is well tolerated in rats and favors the further evaluation of this administration route, including clinical trials.
本研究评估了吸入雾化钆喷酸葡胺的药代动力学及潜在毒性。通过在吸入雾化钆喷酸葡胺(0.25 mol/L)5分钟之前及之后长达36小时的时间内,对肺、血液、尿液及肝脏进行体外弛豫测量来评估药代动力学。为评估潜在毒性,在吸入期间及吸入后10分钟监测血流动力学变量。在暴露前后测量血管外肺水。最后,通过组织学评估组织损伤的可能性。雾化钆喷酸葡胺的肺清除呈单指数形式,半衰期为2.16小时。如尿T1降低所示,雾化钆喷酸葡胺通过肾脏排泄。肾脏清除在30小时内完成。未显示出急性血流动力学效应、组织学变化或水肿诱导。本研究表明,大鼠对吸入雾化钆喷酸葡胺耐受性良好,有利于对该给药途径进行进一步评估,包括临床试验。