Abstract
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 (t 1/2α,t 1/2β), 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%.
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Supported by National Cancer Institute contract NO1-CM-97618, Department of Health and Human Services
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Reid, J.M., Benson, J.W., Viallet, J. et al. Preclinical pharmacology of cholera toxin. Cancer Chemother. Pharmacol. 36, 115–120 (1995). https://doi.org/10.1007/BF00689194
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DOI: https://doi.org/10.1007/BF00689194