title: Pharmacokinetics and tissue distribution of two novel isomerism anticancer platinum compounds.
abstract: 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.
authors.affiliation: a School of Pharmaceutical Sciences , Tsinghua University , Beijing , China ;
authors.forename: Donglin
authors.initials: D
authors.lastname: He
authors.affiliation: b The Second Military General Hospital of Chinese Republic People's Liberation Army , Beijing , China ;
authors.forename: Shuhui
authors.initials: S
authors.lastname: Yin
authors.affiliation: a School of Pharmaceutical Sciences , Tsinghua University , Beijing , China ;
authors.forename: Fuguo
authors.initials: F
authors.lastname: Han
authors.affiliation: a School of Pharmaceutical Sciences , Tsinghua University , Beijing , China ;
authors.forename: Jingjie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: c Dongzhimen Hospital, Beijing University of Chinese Medicine , Beijing , China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.affiliation: a School of Pharmaceutical Sciences , Tsinghua University , Beijing , China ;
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Tong
authors.affiliation: a School of Pharmaceutical Sciences , Tsinghua University , Beijing , China ;
authors.forename: Qingfei
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D007536:Isomerism; D051379:Mice; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D017671:Platinum Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; C561416:LLC-0601; D009944:Organoplatinum Compounds; D017671:Platinum Compounds
keywords: Isomerism antitumor platinum compounds; LLC-0601(R,R); LLC-0601(S,S); pharmacokinetics; tissue distribution