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Pharmacokinetics and metabolism of hexamethylmelamine in mice bearing renal cell tumors

  • Original Articles
  • Pharmacokinetics, Hexamethylmelamine, Renal Cell Tumors
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Summary

The pharmacokinetics of hexamethylmelamine (HMM) and its main metabolites hydroxymethylpentamethylmelamine (HMPMM), pentamethylmelamine (PMM), and 2,2,4,6 tetramethylmelamine (2,2,4,6 TetrMM) were studied in renal cell (RC) tumor tissues and plasma of CDF1 mice that had received IP bolus injections of the maximally tolerated dose (200 mg/kg) of HMM. HMM, PMM, and 2,2,4,6 Tetr MM concentrations determined in RC tissues were much higher than the plasma values, as indicated by the pharmacokinetic parameters (Cmax and AUC). On the other hand, very low levels of HMPMM, generally considered to be a potentially active antitumor compound, were detected in the target tissues, whereas this hydroxylated metabolite was stable and easily determined in plasma. High HMM concentrations in RC tissues could correlate with the high sensitivity of the tumor to this drug. However, the behavior of HMPMM remains unclear; related hypotheses are presented in this paper.

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Authors and Affiliations

  1. Institute de Pharmacie Unité de Toxicologie et de chimie bioanalytique, Université Libre de Bruxelles, Boulevard du Triomphe, CP 205/1, B-1050, Bruxelles, Belgium

    G. Atassi & M. Hanocq

  2. Laboratoire de Pharmacologie cellulaire, Université Libre de Bruxelles Institut de Pharmacie, B-1050, Bruxelles, Belgium

    J. Dubois & F. Abikhalil

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  1. J. Dubois
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  2. G. Atassi
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  3. M. Hanocq
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  4. F. Abikhalil
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Dubois, J., Atassi, G., Hanocq, M. et al. Pharmacokinetics and metabolism of hexamethylmelamine in mice bearing renal cell tumors. Cancer Chemother. Pharmacol. 22, 282–288 (1988). https://doi.org/10.1007/BF00254232

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  • DOI: https://doi.org/10.1007/BF00254232

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