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

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. T max 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 porphyrin HSJ-0017 Tissue distribution Pharmacokinetics Excretion HPLC 

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

Notes

Acknowledgments

The authors would like to thank Dr. Xian-Jun Qu for his valuable assistance in the preparation of the manuscript. This work was supported in part by Natural Science Foundation of Shandong Province (No. 2009ZRB019AO).

Conflict of interest

The authors report no conflict of interest. The authors are responsible for the content and writing of the paper.

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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

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