Allard M, Doucet D, Kien P, Bonnemain B, Caillé J M
Service de Neuroradiologie, Groupe Hospitalier Pellegrin-Tripode, Bordeaux, France.
Invest Radiol. 1988 Sep;23 Suppl 1:S271-4. doi: 10.1097/00004424-198809001-00059.
Pharmacokinetic and acute-toxicity studies of Gd-DOTA meglumine (Mgl) were evaluated in various animals and compared with those of Gd-DTPA Mgl. The agents were injected intravenously at two dosages: 0.1 or 0.5 mmol/kg. Various organs and tissues were removed at specified times after injection and assayed for gadolinium (Gd) concentration. The two complexes behave in an identical fashion in their short-term biodistribution and excretion. The very rapid distribution in the body (except in the brain) and the high clearance from blood are due to an extravascular distribution. The small distribution volume and the very high hydrophilicity account for its extracellular localization. There is no accumulation within any organ. Rapid disappearance, short half-life, size, and hydrophilicity of these molecules are in agreement with urinary elimination by free glomerular filtration. Whatever the species or the salt used, Gd-DOTA appears safer in its acute toxicity than Gd-DTPA with an 85% higher safety factor. These results can be explained by the greater stability of Gd-DOTA (very slow kinetics of dissociation and greater specificity of DOTA than DTPA for gadolinium), and the lower osmolality of DOTA than DTPA. The pharmacokinetic characteristics and the very low toxicity of Gd-DOTA Mgl may prove its suitability for intravenous or oral administration in humans.
对钆喷酸葡甲胺（Mgl）进行了药代动力学和急性毒性研究，并在多种动物中进行了评估，并与钆喷替酸葡甲胺（Gd-DTPA Mgl）的研究结果进行了比较。以两种剂量静脉注射这些药物：0.1或0.5 mmol/kg。在注射后的特定时间取出各种器官和组织，并测定钆（Gd）浓度。这两种复合物在其短期生物分布和排泄方面表现出相同的方式。在体内（脑除外）的快速分布和从血液中的高清除率是由于血管外分布。小的分布容积和非常高的亲水性解释了其细胞外定位。任何器官内均无蓄积。这些分子的快速消失、短半衰期、大小和亲水性与通过自由肾小球滤过的尿液排泄一致。无论使用何种物种或盐，钆喷酸（Gd-DOTA）在急性毒性方面似乎比钆喷替酸（Gd-DTPA）更安全，安全系数高85%。这些结果可以用钆喷酸（Gd-DOTA）的更高稳定性（解离动力学非常缓慢，且DOTA对钆的特异性高于DTPA）以及DOTA的渗透压低于DTPA来解释。钆喷酸葡甲胺（Gd-DOTA Mgl）的药代动力学特征和极低毒性可能证明其适用于人体静脉或口服给药。
