Normann P T, Hals P A
Research and Development, Nycomed Imaging AS, Oslo, Norway.
Eur J Drug Metab Pharmacokinet. 1995 Oct-Dec;20(4):307-13. doi: 10.1007/BF03190250.
The stability and excretion of [14C]-gadodiamide (GdDTPA-BMA) was studied in male rats after i.v. injection of 0.3 mmol/kg [14C]-GdDTPA-BMA (Gd-diethylenetriaminepentaacetic-acid-bis-methylamide) formulated as gadodiamide injection (OMNISCAN, Nycomed Imaging AS, Oslo, Norway). Samples of blood and urine obtained within 60 min and 6 h postdosing, respectively, were analyzed for radiolabeled compounds. Analysis of GdDTPA-BMA in high and low molecular weight fractions of serum indicated no protein binding. HPLC analyses of urine samples obtained 0-2 h, 2-4 h and 4-6 h after injection revealed no detectable amounts of biotransformation products of GdDTPA-BMA. Serum samples obtained 30 min and 60 min after injection contained 9-13 microM of an unidentified compound which had a retention time different from all conceivable metabolites of gadodiamide. A similar concentration of this unknown compound was found in spiked predose serum samples. The total amount of the unknown compound in serum was less than 1% of the injected dose of [14C]-gadodiamide injection. It is concluded that gadodiamide, when administered i.v. as gadodiamide injection at a dosage of 0.3 mmol/kg, is stable in vivo and that the very major part of the dose (> 99%) is excreted in urine as an unchanged complex.
在雄性大鼠静脉注射0.3 mmol/kg的[14C] - 钆双胺（GdDTPA - BMA，即钆喷酸双甲胺，以钆双胺注射液（OMNISCAN，奈科明影像公司，挪威奥斯陆）的形式配制）后，研究了[14C] - 钆双胺的稳定性和排泄情况。分别在给药后60分钟内和6小时采集血液和尿液样本，分析其中的放射性标记化合物。血清高分子量和低分子量组分中钆双胺的分析表明不存在蛋白质结合。对注射后0 - 2小时、2 - 4小时和4 - 6小时采集的尿液样本进行高效液相色谱分析，未发现可检测量的钆双胺生物转化产物。注射后30分钟和60分钟采集的血清样本中含有9 - 13 microM的一种未知化合物，其保留时间与钆双胺所有可能的代谢产物均不同。在加标的给药前血清样本中也发现了类似浓度的这种未知化合物。血清中未知化合物的总量低于[14C] - 钆双胺注射液注射剂量的1%。结论是，当以0.3 mmol/kg的剂量静脉注射钆双胺注射液时，钆双胺在体内是稳定的，并且剂量的绝大部分（> 99%）以未变化的复合物形式经尿液排泄。
