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

[ Vol. 18 , Issue. 5 ]

Author(s):

Yu Mingming, Wang Yuanhong, Ma Fugang, Yu Weijie, Jiang Tingfu and LV Zhihua   Pages 391 - 399 ( 9 )

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.

Affiliation:

Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003

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