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薬物担体としての多糖類 : フルオレセイン標識デキストランのマウスにおける体内動態 Polysaccharides as Drug Carriers : Biodisposition of Fluorescein-Labeled Dextrans in Mice 金尾, 義治 上村, 智哉 田中, 哲郎 加納, 聰 P(論文) 分子量の異なるフルオレセイン標識デキストラン(FD)のマウスにおける体内動態を評価した.分子量20kDa未満のFDは血中から速やかに消失し,肝への分布は低かった.より高い分子量をもつFDは顕著に肝へ分布し,長期にわたって蓄積した.肝平均滞留時間は22.5～28.1日であった.肝に蓄積したFDの一部は低分子化を受けた.肝取込みクリアランスは分子量の増加に伴って減少した.尿中並びに糞便中排泄にも顕著な分子量依存性が認められた.肝取込みには顕著な投与量依存性が観察された.みかけのKm(投与量)とVmax(肝臓のレベル)の値は,それぞれ116±5mg/kg並びに1.10±0.05mg/g tissueと算出された. The biodisposition of fluorescein-labeled dextrans (FDs) with different molecular weights (MW = 4-500 kDa) was systematically examined in mice. After intravenous injection of FDs at a dose of 120 mg/kg, the levels of FDs in the blood circulation and in the various organs were measured fluorometrically. FDs with a molecular weight lower than 20 kDa showed poor hepatic distribution (2.1-3.7 % of dose/g tissue) due to their rapid elimination from the blood circulation. FDs with higher molecular weights were appreciably distributed in the liver (18.9-24.0 % of dose/g tissue) and accumulated there over a long period, whereas the FD levels in the other organs were almost negligible a few days after injection. The hepatic mean residence time of FDs ranged from 22.5 to 28.1 d. Partial depolymerization of FDs which accumulated in the liver was observed within 10 d after administration. The hepatic uptake clearance of FDs was decreased with an increase in molecular weight. A marked molecular weight dependency was also seen in the urinary and fecal excretions of FDs. An appreciable dose-dependency was demonstrated in the hepatic uptake of FDs (MW = 40 kDa) , as well. The amount of hepatic uptake as a function of dose showed saturation kinetics and was analyzed by a Michaelis-Menten type equation. The apparent values of Km (dose) and Vmax (hepatic level) estimated were 116 ± 5 mg/kg and 1.10 ± 0.05 mg/g tissue, respectively. 1998 jpn departmental bulletin paper https://fukuyama-u.repo.nii.ac.jp/records/7091 AN10064550 福山大学薬学部研究年報 Annual report of the Faculty of Pharmacy & Pharmaceutical Sciences, Fukuyama University 16 84 85 https://fukuyama-u.repo.nii.ac.jp/record/7091/files/KJ00005784688.pdf application/pdf 71.9 kB 1998-01-01