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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 - 1977
Externally publishedYes

Fingerprint

alanosine
Haplorhini
Dogs
Asparagine
Glutamine
Radioactivity
Half-Life
Pharmaceutical Preparations
Homoserine
Kidney
Isoleucine
Liver
Valine
Enzyme Assays
Threonine
Carbon Monoxide
Leucine
Serine
Small Intestine
Cysteine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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.

Pharmacologic disposition of DL-alanosine in mice, rats, dogs, and monkeys. / Kelley, J. M.; Adamson, R. H.; Cooney, D. A.; Jayaram, H. N.; Anandaraj, S.

In: Cancer Treatment Reports, Vol. 61, No. 8, 1977, p. 1471-1484.

Research output: Contribution to journalArticle

Kelley, JM, Adamson, RH, Cooney, DA, Jayaram, HN & Anandaraj, S 1977, 'Pharmacologic disposition of DL-alanosine in mice, rats, dogs, and monkeys', Cancer Treatment Reports, vol. 61, no. 8, pp. 1471-1484.
Kelley JM, Adamson RH, Cooney DA, Jayaram HN, Anandaraj S. Pharmacologic disposition of DL-alanosine in mice, rats, dogs, and monkeys. Cancer Treatment Reports. 1977;61(8):1471-1484.
Kelley, J. M. ; Adamson, R. H. ; Cooney, D. A. ; Jayaram, H. N. ; Anandaraj, S. / Pharmacologic disposition of DL-alanosine in mice, rats, dogs, and monkeys. In: Cancer Treatment Reports. 1977 ; Vol. 61, No. 8. pp. 1471-1484.
@article{0585f31a82a54c90a1126cc97a9ea8d9,
title = "Pharmacologic disposition of DL-alanosine in mice, rats, dogs, and monkeys",
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.",
author = "Kelley, {J. M.} and Adamson, {R. H.} and Cooney, {D. A.} and Jayaram, {H. N.} and S. Anandaraj",
year = "1977",
language = "English (US)",
volume = "61",
pages = "1471--1484",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - Pharmacologic disposition of DL-alanosine in mice, rats, dogs, and monkeys

AU - Kelley, J. M.

AU - Adamson, R. H.

AU - Cooney, D. A.

AU - Jayaram, H. N.

AU - Anandaraj, S.

PY - 1977

Y1 - 1977

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0017707214&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0017707214&partnerID=8YFLogxK

M3 - Article

VL - 61

SP - 1471

EP - 1484

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 8

ER -