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  • Title: Toxicology and pharmacokinetics of (1,1-bis(aminomethyl)cyclohexane)oxalatoplatinum(II) (TNO-38).
    Author: Lelieveld P, van der Vijgh WJ, van Velzen D.
    Journal: Eur J Cancer Clin Oncol; 1986 Dec; 22(12):1467-73. PubMed ID: 3595672.
    Abstract:
    Preclinical studies on toxicology and pharmacokinetics were performed for (1,1-bis(aminomethyl)cyclohexane)oxalatoplatinum(II) (TNO-38) in rats and a dog after LD10 and LD50 assessment in mice. In drug-treated rats, ura and creatinine concentrations were 1.4-1.9 times those in control rats. Histopathology showed necrosis of tubular epithelium of the kidneys, which was comparable to damage observed after treatment with cisplatin (CDDP), and extensive necrosis of crypt epithelium, especially in the ileum. Similar to CDDP, TNO-38 was emetic in the dog. Non-specific subacute inflammatory changes were observed in the ileum. Renal damage was much less pronounced. Half-lives of distribution and elimination were 6.2 min and 5.2 days, respectively. The cumulative excretion of Pt in urine over 1 and 7 days after drug treatment was 38.3 and 49.3% of the dose, respectively. Twelve weeks after drug administration, Pt concentrations were highest in kidneys and liver. TNO-38 is adequately water soluble. Its reported antitumour activity is consistently lower than that of CDDP. The drug's toxicity was, in general, comparable to that of CDDP. Its pharmacokinetic profile was very similar to that of CDDP. It is concluded that TNO-38 should probably not be further evaluated in clinical studies.
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