Kurtzhals P, Larsen C
Acta Pharm Nord. 1989;1(4):201-10.
The plasma half life and the urinary recovery after i.v. administration to rabbits (35 mg/kg) of FITC-dextrans and naproxen-dextran ester prodrugs of molecular weights 40,000 and 70,000 were determined by employing a HP(SEC) procedure with fluorescence detection. The conjugates disappeared from the blood stream roughly according to first-order kinetics at a rate only slightly influenced by the molecular weight and faster than the parent carrier dextrans. 15-30% of the dose of the derivatives was eliminated through the kidneys as compared to 44% (T-40) and 17% (T-70) of the parent dextrans. Liver uptake of the compounds was assumed to be the main additional elimination pathway as 46% of an i.v. dose of FITC dextran T-70 was found in the liver four hours after the injection, whereas only minor amounts were detected in the spleen, lungs and the kidneys. The molecular weight distribution of the conjugates in the circulation shifted continuously in the high molecular weight direction. The role of the liver in plasma clearance of the conjugates and the influence of the molecular weight and electric charge on the in vivo fate of the dextran derivatives are discussed.
通过采用带荧光检测的高效液相色谱（HP(SEC)）方法，测定了分子量为40,000和70,000的FITC-葡聚糖和萘普生-葡聚糖酯前药静脉注射给兔子（35mg/kg）后的血浆半衰期和尿回收率。这些缀合物从血流中消失大致符合一级动力学，其速率仅受分子量的轻微影响，且比母体载体葡聚糖更快。与母体葡聚糖的44%（T-40）和17%（T-70）相比，衍生物剂量的15-30%通过肾脏消除。假定化合物的肝脏摄取是主要的额外消除途径，因为静脉注射FITC葡聚糖T-70剂量的46%在注射后四小时在肝脏中被发现，而在脾脏、肺和肾脏中仅检测到少量。循环中缀合物的分子量分布持续向高分子量方向移动。讨论了肝脏在缀合物血浆清除中的作用以及分子量和电荷对葡聚糖衍生物体内命运的影响。
