Preclinical pharmacology of cholera toxin

Joel M Reid, J. W. Benson, J. Viallet, M. M. Ames

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Cholera toxin was selected for pharmacologic evaluation by the National Cancer Institute on the basis of antiproliferative activity against small-cell and non-small-cell lung-cancer cell lines. A feature common to the sensitive cell lines was abundant expression of G(M1) ganglioside, the cellular receptor for cholera toxin. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to quantitate cholera toxin in biological fluids. A sigmoidal relationship was observed between the cholera toxin plasma concentration and the absorbance at 490 nm (OD490) of the product of horseradish peroxidase-catalyzed oxidation of o-phenylenediamine over the range of 6.25-1,600 ng/ml. Legit transformation of the OD490 data was linear over the entire concentration range and assay variability was less than 25%. Cholera toxin was stable in murine and human whole blood and plasma. Following i.v. administration of 1,500 μg/kg to male CD2F1 mice, cholera toxin plasma elimination was described by a two-compartment open model. The half-lives (t( 1/2 )α, t( 1/2 )β), plasma clearance, and steady-state volume of distribution were 0.7 min, 49 min, 24 ml min-1 kg-1 912 ml/kg, respectively. Cholera toxin was not detected in plasma following an s.c. dose of 1,500 μg/kg. Urinary recovery following intravenous drug administration was less than 0.1%.

Original languageEnglish (US)
Pages (from-to)115-120
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume36
Issue number2
DOIs
StatePublished - 1995

Fingerprint

Cholera Toxin
Pharmacology
Plasmas
Cells
Assays
G(M1) Ganglioside
Immunosorbents
Cell Line
Horseradish Peroxidase
National Cancer Institute (U.S.)
Non-Small Cell Lung Carcinoma
Intravenous Administration
Blood
Enzyme-Linked Immunosorbent Assay
Recovery
Oxidation
Fluids
Enzymes
Pharmaceutical Preparations

Keywords

  • Cholera toxin
  • Immunoassay
  • Pharmacokinetics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology

Cite this

Preclinical pharmacology of cholera toxin. / Reid, Joel M; Benson, J. W.; Viallet, J.; Ames, M. M.

In: Cancer Chemotherapy and Pharmacology, Vol. 36, No. 2, 1995, p. 115-120.

Research output: Contribution to journalArticle

Reid, Joel M ; Benson, J. W. ; Viallet, J. ; Ames, M. M. / Preclinical pharmacology of cholera toxin. In: Cancer Chemotherapy and Pharmacology. 1995 ; Vol. 36, No. 2. pp. 115-120.
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