Pharmacokinetics, Tissue Distribution and Excretion Study of Fluorescein-labeled PS916 in Rats

Author(s): Yu Mingming , Wang Yuanhong , Ma Fugang , Yu Weijie , Jiang Tingfu , LV Zhihua* .

Journal Name: Current Pharmaceutical Biotechnology

Volume 18 , Issue 5 , 2017

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Abstract:

Background: PS916, chitosan derivative with shown activities in atherosclerotic and fatty liver, is being investigated as an anti-atherosclerotic agent in clinical trials in China.

Methods: Fluorescein-labeled PS916 (PS916-FTC) was prepared by the reaction with fluorescein isothiocyanate. The pharmacokinetics and bio-disposition of PS916-FTC were studied in rats after oral or intravenous administration.

Results: Analysis of the plasma, urine, fecal and tissue samples collected at intervals up to 72 h revealed that PS916-FTC exhibited moderate volume of distribution (Vss, 0.650~0.748 L/kg), and low clearance (60.9~107 mL/h/kg) after intravenous administration. The pharmacokinetics of PS916-FTC was characterized by low bioavailability (8.40%) after oral administration. The average accumulation ratio for PS916-FTC exposure after steady-state administration was 1.04. A two-compartmental pharmacokinetics model was employed. The urinary route was the major pathway (54.4%), and the fecal route was a minor pathway (6.29%) for PS916-FTC elimination after intravenous administration; the fecal route was the major pathway (79.0%) for PS916-FTC elimination after oral administration.

Conclusion: PS916-FTC was widely distributed to most tissues in rats; relatively high levels of PS916-FTC in kidney and liver were observed after intravenous or oral administration. These findings supported the understanding of pharmacokinetics and bio-disposition of PS916 in rats and provide relevant information for future design of clinical studies.

Highlights: 1) Fluorescein-labeled PS916 was successfully synthesized. 2) A rapid and sensitive analytical method of PS916-FTC was validated. 3) The pharmacokinetic of PS916-FTC in rats was investigated. 4) The bio-distribution of PS916-FTC in rats was investigated.

Keywords: PS916-FTC, chitosan derivatives, pharmacokinetics, tissue distribution, spectrofluorometer, hyperlipidemia.

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Article Details

VOLUME: 18
ISSUE: 5
Year: 2017
Page: [391 - 399]
Pages: 9
DOI: 10.2174/1389201018666170425120832
Price: $58

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