Pharmacokinetics and tissue distribution of two novel isomerism anticancer platinum compounds

Drug Dev Ind Pharm. 2016 Nov;42(11):1792-9. doi: 10.3109/03639045.2016.1173053. Epub 2016 Apr 24.


LLC-0601(S,S) and LLC-0601(R,R) are two novel synthesized isomerism platinum compounds both with encouraging anticancer activity. However, the previous study showed that toxicity of LLC-0601(R,R) was much higher than that of LLC-0601(S,S) with higher body weight loss and mortality rate of tested rats. This paper is focused on the comparison of the two compounds with their pharmacokinetic (PK) profiles in rats and tissue distribution in mice after intravenous administration. The atomic absorption spectrometry (AAS) method was successfully developed and applied for the determination of platinum in plasma and tissues. The results showed that main PK parameters such as half-life, AUC and MRT of the two compounds had no significant difference after intravenous administration to rats (p > 0.05). The tissue distribution after intravenous administration to mice showed that the concentration of LLC-0601(R,R) in heart at 0.083 h was higher than that of LLC-0601(S,S) (p < 0.05) and it was the same case for AUC5min-4 h (p < 0.05). Different distribution of the two compounds in heart was possibly the main reason of different toxicity and more in-depth research on the metabolites and other mechanism are needed to investigate the toxicity.

Keywords: Isomerism antitumor platinum compounds; LLC-0601(R,R); LLC-0601(S,S); pharmacokinetics; tissue distribution.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics*
  • Isomerism
  • Mice
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacokinetics*
  • Platinum Compounds / chemistry
  • Platinum Compounds / pharmacokinetics*
  • Rats
  • Tissue Distribution


  • Antineoplastic Agents
  • LLC-0601
  • Organoplatinum Compounds
  • Platinum Compounds