Cancer Chemotherapy and Pharmacology

, Volume 36, Issue 2, pp 115–120 | Cite as

Preclinical pharmacology of cholera toxin

  • Joel M. Reid
  • John W. Benson
  • Jean Viallet
  • Matthew M. Ames
Original Article Holera Toxin, Immunoassay, Pharmacokinetics


Cholera toxin was selected for pharmacologic evaluation by the National Cancer Institute on the basis of antiproliferative activity against small-cell and nonsmall-cell lung-cancer cell lines. A feature common to the sensitive cell lines was abundant expression of GM1 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 ofo-phenylenediamine over the range of 6.25–1,600 ng/ml. Logit 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 (t1/2α,t1/2β), 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%.

Key words

Cholera toxin Immunoassay Pharmacokinetics 


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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Joel M. Reid
    • 1
  • John W. Benson
    • 1
  • Jean Viallet
    • 2
  • Matthew M. Ames
    • 1
  1. 1.Department of Oncology, Division of Developmental Oncology ResearchMayo Clinic and FoundationRochesterUSA
  2. 2.Department of OncologyMcGill University and Montreal General HospitalMontrealCanada

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