Long - Term Toxicity Of Nitrosol And Its Pharmacokinetics

Nifurtimox is an I type chemical drug for the treatment of tumors developed by Hengtaijiukang(Tianjin) Pharmaceutical Technology Co., LTD. First, we had an study of nifurtimox on the long-term toxicity in SD rats and Beagle dogs to test the drug’s indicators such as hematology, histopathology, and to ensure the safety of the drug doses. We also took the preliminary concomitant toxicokinetics research to observe exposure condition of an ex-therapeutic doses and strengthen the reliability of drug toxicity prediction for providing important guidance for clinical use.The No Observed Effective Level(NOEL) of nifurtimox in SD rats is 25mg·kg-1. It showed toxic response at dose of 75 and 150mg·kg-1, and the main toxic target organs are spleens of the female, testes and epididymides of the male and the nervous system, the lesion is not reversible. The results of the toxicokinetics research showed that after a medication in SD rats for 4 weeks, there was an accumulation at each does level in female rats, and only showed an accumulation at the medium does in the male rats. There was no accumulation at the low and high-does group in the male rats. There showed a full exposure at each dose group, and basically achieved a maximum exposure at the high does in both male and female rats. Additionally, there was a difference of exposure of nifurtimox in different gender.In research of Beagle dogs’ 28-day-long-term-toxicity experiment and its concomitant toxicokinetics, the male animals of each does group showed pathologic changes of testes and epididymides with the main forms of testicular atrophy, deciduous sperm cells in seminiferous tubule, no long sperm and the empty epididymis pipe, the lesion is not reversible,either. The results of the toxicokinetics research showed that after a medication in Beagle dogs for 4 weeks, there was no obvious accumulation at the low and medium does group in Beagle dogs. But the high-does group had showed an accumulation. There showed a full exposure at each dose group, and basically achieved a maximum exposure at medium and high does in both male and female rats. Nifurtimox had a similar exposure in different gender.