Schuhmann-Giampieri G, Frenzel T, Schmitt-Willich H
Schering Aktiengesellschaft, Contrast Media Research, Berlin, Fed. Rep. of Germany.
Arzneimittelforschung. 1993 Aug;43(8):927-31.
The introduction of the lipophilic moiety, ethoxybenzyl, into the gadolinium chelate dimeglumine gadopentetate (Gd-DTPA, Magnevist, CAS 86050-77-3) yielded (4S) 4-(4-ethoxybenzyl)-3,6,9-tris (carboxylatomethyl)-3,6,9-triazaundecandioic acid, gadolinium complex, disodium salt (Gd-EOB-DTPA), a compound with a potential as a magnetic resonance contrast agent for liver mass screening. Both in the rat and in the dog the pharmacokinetics of Gd-EOB-DTPA were nonlinear in the dose range of 0.05-0.5 mmol/kg (rat) and 0.03-0.25 mmol/kg (dog) since after correction for the difference in dose the plasma concentration-time profiles were not superimposable and the amounts excreted renally and fecally differed significantly (p < 0.05). Extrarenal elimination played an important role since fecal elimination (% of dose) was 73.4 +/- 5.6 in rats (0.05 mmol/kg), 70.1 +/- 4.0 in dogs (0.03 mmol/kg) and 32.1 +/- 6.4 in monkeys (0.25 mmol/kg). However, in all species investigated, the values of renal clearance (Clr) were independent of dose and close to the value of the glomerular filtration rate (Clr in ml/min.kg: 10.4 +/- 3.5 in rats; 3.88 +/- 0.8 in dogs; 1.01 +/- 0.3 in monkeys). Therefore, the pharmacokinetics of Gd-EOB-DTPA can best be described by a capacity-limited transport process via the biliary route of elimination thus strongly resembling the pharmacokinetics of some biliary X-ray contrast media (iotroxic, iodipamic or idoxamic acid) or the synthetic dyes (indocyanine green). However, contrary to the latter agents the plasma binding (%) of Gd-EOB-DTPA was low in all species (10.3 +/- 1.4 in rats: 10.0 +/- 1.3 in dogs; 17.5 +/- 1.0 in monkeys).
将亲脂性部分乙氧基苄基引入钆螯合物钆喷酸葡甲胺（Gd-DTPA，马根维显，CAS 86050-77-3）后，得到了（4S）4-（4-乙氧基苄基）-3,6,9-三（羧甲基）-3,6,9-三氮杂十一烷二酸钆络合物二钠盐（Gd-EOB-DTPA），一种具有作为肝脏肿块筛查磁共振造影剂潜力的化合物。在大鼠和犬中，Gd-EOB-DTPA在0.05 - 0.5 mmol/kg（大鼠）和0.03 - 0.25 mmol/kg（犬）的剂量范围内药代动力学呈非线性，因为在校正剂量差异后，血浆浓度-时间曲线无法叠加，经肾和经粪便排泄的量有显著差异（p < 0.05）。肾外消除起重要作用，因为在大鼠（0.05 mmol/kg）中粪便排泄（占剂量的百分比）为73.4 ± 5.6，在犬（0.03 mmol/kg）中为70.1 ± 4.0，在猴（0.25 mmol/kg）中为32.1 ± 6.4。然而，在所有研究的物种中，肾清除率（Clr）的值与剂量无关，且接近肾小球滤过率的值（Clr以ml/min.kg计：大鼠为10.4 ± 3.5；犬为3.88 ± 0.8；猴为1.01 ± 0.3）。因此，Gd-EOB-DTPA的药代动力学最好用通过胆汁排泄途径的容量限制转运过程来描述，这与一些胆汁X射线造影剂（碘托酸、碘帕醇或碘多酸）或合成染料（吲哚菁绿）的药代动力学非常相似。然而，与后一类药物相反，Gd-EOB-DTPA在所有物种中的血浆蛋白结合率（%）都很低（大鼠为10.3 ± 1.4；犬为10.0 ± 1.3；猴为17.5 ± 1.0）。
