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The comparative pharmacokinetics of pentamethylmelamine in man, rat, and mouse

  • Original Articles
  • Pentamethylmelamine Pharmacokinetics
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Summary

The pharmacokinetics of pentamethylmelamine (PMM) have been investigated in mouse (Balb C-, CBA/LAC, nude), rat (Wistar), and man. In all three species, PMM was extensively demethylated to N2,N2,N4,N6-tetramethylmelamine and N2,N4,N6-trimethylmelamine, although marked species differences in the rate of metabolism were observed. PMM metabolism was more rapid in the mouse (plasma t1/2 =<15 min) than in the rat (plasma t1/2=40 min), and slower in man (plasma t1/2=102 min) than in either mouse or rat. Furthermore, the peak plasma concentrations of N-methylolmelamines, intermediates generated during oxidative N-demethylation, were correspondingly higher in the mouse (563–773 μM) than in the rat (211 μM), whilst in man they were undetectable (<50 μM). In view of the highly cytotoxic nature of N-methylolmelamines, we conclude that these pharmacokinetic differences may be related to the antitumour effectiveness of PMM in mouse, rat, and man.

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Authors and Affiliations

  1. Department of Biochemical Pharmacology, Institute of Cancer Research, Block E, Clifton Avenue, Belmont, Sutton, Surrey, Great Britain

    C. J. Rutty, D. R. Newell, J. R. F. Muindi & K. R. Harrap

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  1. C. J. Rutty
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  2. D. R. Newell
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  3. J. R. F. Muindi
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  4. K. R. Harrap
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Rutty, C.J., Newell, D.R., Muindi, J.R.F. et al. The comparative pharmacokinetics of pentamethylmelamine in man, rat, and mouse. Cancer Chemother. Pharmacol. 8, 105–111 (1982). https://doi.org/10.1007/BF00292880

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  • DOI: https://doi.org/10.1007/BF00292880

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