Pharmacokinetics and biodisposition of poly(vinyl alcohol) in rats and mice.
Pharmacokinetics and biodisposition of poly(vinyl alcohol) in rats and mice.
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DOI：
10.2133/dmpk.20.435
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发表时间：
2005-12-01
影响因子：
2.1
通讯作者：
Ikeda, Yuka
中科院分区：
文献类型：
--
作者：
Kaneo, Yoshiharu;Hashihama, Shiori;Ikeda, Yuka
Poly(vinyl alcohol) (PVA) of various molecular weight (MW=10,560-116,600) was successfully labeled with fluorescein isothiocyanate isomer I (FITC) according to the method of de Belder and Granath. A high-performance size-exclusion chromatographic procedure was developed for the quantitative analysis of FITC-labeled poly(vinyl alcohol) (F-PVA) in biological samples. F-PVA (80 K) disappeared slowly from the blood circulation according to the first-order kinetics (t1/2=7 h) after intravenous injection to rats. A dose-independent behavior of F-PVA (80 K) was observed in the blood circulation, in the tissue distribution and in the urinary and fecal excretions. This suggested that PVAs are eliminated exclusively by the mechanisms that do not involve saturable transport processes. Furthermore, it was found that PVAs are very stable in the body because no degradation product was detected in the urine and feces. 125I-labeled poly(vinyl alcohol) (125I-PVA) was prepared by introducing tyramine residues to the hydroxyl groups of PVA molecules by the 1,1'-cabonyldiimidazole (CDI) activation method. 125I-PVA (80 K) was retained in the blood circulation for several days after intravenous injection to mice. Although the tissue distribution of PVAs was small, a significant accumulation into the liver and the spleen was observed. Fluorescence microscopic examination of paraffin section of the liver revealed that F-PVA (80 K) was endocytosed by the liver parenchymal cells. 125I-PVA (80 K) captured by liver was slowly transported via the bile canaliculi and gall bladder to the intestine and excreted in the feces. It was suggested, therefore, a long time is necessary for 125I-PVA (80 K) to be excreted perfectly from the body.
