Pharmacokinetics and tissue distribution in rats of a novel anticancer platinum compound LLC-1903

Abstract

1. LLC-1903, a novel anticancer compound, was synthesized by optimizing the structure, which was derived from altering the leaving group of lobaplatin. It has an excellent in vitro anti-cancer activity, high water solubility, high stability in solution and low in vivo toxicity according to our former study.

2. The plasma pharmacokinetics (PK) and tissue distribution of LLC-1903 and lobaplatin in rats were determined after intravenous administration of a single dose (0.06 mmol/kg body weight). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of platinum (Pt) in plasma and tissue samples.

3. Most PK parameters of the Pt in LLC-1903 showed a significant difference from those of lobaplatin. The plasma level of LLC-1903 is only half of that of lobaplatin (p < 0.01) which could be the direct result of faster drug clearance. The tissue distribution showed that both LLC-1903 and lobaplatin were mainly found in the liver and kidney, and less in other organs. At four time points (0.083, 0.5, 1 and 4 h) after administration, the tissue concentrations of LLC-1903 were almost always significantly higher than those of lobaplatin (p < 0.05 or p < 0.01).

Keywords:

• Anti-cancer platinum compound
• LLC-1903
• lobaplatin
• pharmacokinetics
• tissue distribution

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Acknowledgement

The authors thank Prof. Walter Luyten, KU Leuven, for his kind help in improving English of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the State Key Laboratory of Advanced Technologies for Comprehensive Utilization of Platinum Metals [grant number SKL-SPM-201802], Yunnan Science and Technology Project [grant number 2017ZF010] and National Natural Science Foundation of China [grant number 21661018].