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Release of methyl isocyanate from the antitumor agent caracemide (NSC-253272)

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Abstract

In recent phase 1 clinical trials, caracemide [N-acetyl-N-(methylcarbamoyloxy)-N-methylurea; NSC-253272] has demonstrated a marked potential to produce severe central nervous system (CNS) toxicity. Recent in vitro studies of this antitumor agent have presented indirect evidence indicating that methyl isocyanate is a likely metabolite which results from incubation of caracemide with either phosphate buffer or human plasma [4]. This report presents evidence that methyl isocyanate is formed from caracemide in a concentration- and time-dependent manner. These data implicate the caracemide-mediated formation of methyl isocyanate as at least a plausible explanation for the CNS toxicity exhibited by this drug.

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References

  1. Clinical brochure “Caracemide NSC 253272,” Division of Cancer Treatment, National Cancer Institute, 1983

  2. Adams F, Kavanagh J, Raber M: Neuropsychiatric manifestations of caracemide toxicity in a phase I trial. (Abstr) Am Soc Clin Onc 4:50, 1985

    Google Scholar 

  3. Newman RA, Farquhar D, Lu K: Biochemical pharmacology of Caracemide. (Abstr) Proc Am Assoc Cancer Res 26:258, 1985

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  4. Newman RA, Farquhar D, Lu K: Biochemical pharmacology of N-acetyl-N-(methylcarbamoyloxy)-N′-methylurea (Caracemide: NSC-253272) Biochem Pharmacol 35:2781–2787, 1986

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  5. Lu K, Savaraj N, Feun LG: Pharmacokinetics of caracemide (CAR, NSC-253272) in dogs. (Abstr) Proc of Am Assoc Cancer Res 26:359, 1985

    Google Scholar 

  6. Johnston TP, McCaleb GS, Montgomery JA: The synthesis of antineoplastic agents. XXXII: N-Nitrosoureas. J Med Chem 6:669, 1963

    Google Scholar 

  7. Raghuveeran CD, Kaushik MP: Reversed-phase high- performance liquid chromatography of methyl isocyanate. J Chromatogr 346:446–449, 1985

    Google Scholar 

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Authors and Affiliations

  1. Department of Medical Oncology, Section of Pharmacology, U.T.M.D. Anderson Hospital and Tumor Institute, 1515 Holcombe Blvd., 77030, Houston, TX, USA

    Robert A. Newman & David Farquhar

Authors
  1. Robert A. Newman
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  2. David Farquhar
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Newman, R.A., Farquhar, D. Release of methyl isocyanate from the antitumor agent caracemide (NSC-253272). Invest New Drugs 5, 267–271 (1987). https://doi.org/10.1007/BF00175297

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  • DOI: https://doi.org/10.1007/BF00175297

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