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

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

Volume: 18 Issue: 5

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

Affiliation:

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

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

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.

Cite this article as:

Mingming Yu, Yuanhong Wang, Fugang Ma, Weijie Yu, Tingfu Jiang and Zhihua LV*, Pharmacokinetics, Tissue Distribution and Excretion Study of Fluorescein-labeled PS916 in Rats , Current Pharmaceutical Biotechnology 2017; 18 (5) . https://dx.doi.org/10.2174/1389201018666170425120832

DOI https://dx.doi.org/10.2174/1389201018666170425120832	Print ISSN 1389-2010
Publisher Name Bentham Science Publisher	Online ISSN 1873-4316