European Journal of Drug Metabolism and Pharmacokinetics

, Volume 38, Issue 4, pp 245–253

Pharmacokinetics, tissue distribution and excretion of manganese (III) meso-tetra [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride, a novel superoxide dismutase mimic, in Wistar rats

  • Bao-qiu Li
  • Shi-hong Fang
  • Xin Dong
  • Na Li
  • Ji-you Gao
  • Gui-qin Yang
  • Xian-chang Gong
  • Shu-juan Wang
  • Feng-shan Wang
Original Paper

DOI: 10.1007/s13318-013-0118-0

Cite this article as:
Li, B., Fang, S., Dong, X. et al. Eur J Drug Metab Pharmacokinet (2013) 38: 245. doi:10.1007/s13318-013-0118-0

Abstract

Manganese (III) 5, 10, 15, 20-tetrakis [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride, designated HSJ-0017, is a novel superoxide dismutase mimic. It exhibits strong free-radical scavenging activities in vitro and in vivo. The aim of the present study was to investigate the pharmacokinetics, tissue distribution and excretion of HSJ-0017 in Wistar rats following a single intravenous administration. Wistar rats were given different doses of HSJ-0017 by single intravenous injection. Biological samples of rats were collected and were assayed by the HPLC method. The pharmacokinetics, tissue distribution and excretion of HSJ-0017 were investigated. The pharmacokinetic data of HSJ-0017 in rats following intravenous injection was best-fit by a two-compartment model. Tmax of HSJ-0017 in plasma following intravenous injection was 0.083 h. AUC and plasma drug concentration were found to increase in a dose-related fashion. The highest concentrations of HSJ-0017 were detected in the liver (82.25 ± 13.99 μg/g) of rats, followed by the kidney, small intestine, lung, plasma, heart, spleen, and stomach within 2 h postdose. No HSJ-0017 was detected in the uterus, parorchis or brain of rats during the 24-h period of examination. The total cumulative excretion of HSJ-0017 in rat bile and urine were found to be 78.85 and 67.58 %, respectively. Our study has led to the view that the HSJ-0017 can be rapidly distributed to tissues after intravenous administration, but cannot diffuse through the blood–brain barrier. The faecal and biliary excretion of unchanged HSJ-0017 are the major routes of HSJ-0017 elimination.

Keywords

Manganese porphyrinHSJ-0017Tissue distributionPharmacokineticsExcretionHPLC

Abbreviations

SOD

Superoxide dismutase

ROS

Reactive oxygen species

HSJ-0017

Manganese (III) meso-tetra [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride

MnTPPCl

Manganese (III) meso-tetraphenylporphyrin chloride

PK

Pharmacokinetics

RSD

Relative standard deviation

BBB

Blood–brain barrier

Copyright information

© Springer-Verlag France 2013

Authors and Affiliations

  • Bao-qiu Li
    • 1
  • Shi-hong Fang
    • 2
  • Xin Dong
    • 2
  • Na Li
    • 2
  • Ji-you Gao
    • 2
  • Gui-qin Yang
    • 2
  • Xian-chang Gong
    • 3
  • Shu-juan Wang
    • 4
  • Feng-shan Wang
    • 1
  1. 1.School of Pharmaceutical SciencesShandong UniversityJinanChina
  2. 2.Shandong Hongli Laboratory Animal Experiment Co., Ltd.JinanChina
  3. 3.Jinan Saiwen Pharmaceuticals, Inc.JinanChina
  4. 4.Jilin Province A-Think Pharmaceutical Co., Ltd.ChangchunChina