Investigation on pharmacokinetics, tissue distribution and excretion of a novel anticancer platinum compound by inductively coupled plasma mass spectrometry after intravenous administration to rats

摘要

SM54111 [cis-3, 5-diisopropylsalylic cyclohexanodiaminoplatinum (II), Saliplatin] is a novel platinum compound with encouraging anticancer effect. In order to get more useful information in multiple species for the security evaluation, dosage design, and drug delivery design, its pharmacokinetic behaviors in rats after intravenous administration were investigated in this study. Based on its pharmacokinetics in plasma, the distribution of SM54111 in heart, liver, spleen, lung, kidney, brain, adipose, testicle, or ovaries of rats sampled at 0.5 h, 1 h, and 3 h after intravenous administration were determined utilizing inductively coupled plasma mass spectrometry (ICP-MS). Its amounts in urine and feces were determined at 8 sampling times till 96 h as well. It was proved that SM54111 fitted open two-compartment model in rats, with wide distribution in tissues and slow excretion. Its reasonable pharmacokinetic properties in rats make this novel platinum compound worthy of further research and development.