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
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.