Pharmacologic disposition of DL-alanosine in mice, rats, dogs, and monkeys

J. M. Kelley, R. H. Adamson, D. A. Cooney, H. N. Jayaram, S. Anandaraj

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Abstract

The pharmacologic disposition of DL alanosine was studied in mice, rats, dogs, and monkeys. The major portion of the parenterally administered drug was excreted in the urine by all of the species studied; however, in rodents an important fraction of the dose was expired as CO 2. Organs in which DL alanosine accumulates include the kidneys, lungs, liver, and small intestine. Considerable drug derived radioactivity persists for periods up to 14 days in the hepatic and renal parenchyma. Studies on the clearance of DL alanosine in mice using a specific enzymatic assay procedure indicated that the plasma half life of the parent drug was shorter than the half life of total radioactivity. In both cases, however, the kinetics were complex and not readily resolvable into discrete phases. In murine lymphoblasts (L5178Y/AR) the transport of DL alanosine was found to be a sodium stimulated, saturable, and thermosensitive process which was inhibited by L threonine, L asparagine, L glutamine, L serine, L leucine, L isoleucine, L valine, L cysteine, and L homoserine. Kinetic studies on the influence of L asparagine and L glutamine on this transport revealed that the inhibition was competitive in nature.

Original languageEnglish (US)
Pages (from-to)1471-1484
Number of pages14
JournalCancer Treatment Reports
Volume61
Issue number8
StatePublished - Dec 1 1977

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kelley, J. M., Adamson, R. H., Cooney, D. A., Jayaram, H. N., & Anandaraj, S. (1977). Pharmacologic disposition of DL-alanosine in mice, rats, dogs, and monkeys. Cancer Treatment Reports, 61(8), 1471-1484.