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Oltipraz: a laboratory and clinical review
1Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.
Journal of Cellular Biochemistry. Supplement
|January 1, 1993
Summary
Oltipraz, a compound found in cruciferous vegetables, shows promise as a chemopreventive agent by inducing detoxification enzymes and inhibiting cancer in animal models. Human trials indicate a maximum tolerated dose of 125 mg daily, with toxicities including photosensitivity.
Area of Science:
- Chemoprevention
- Drug Development
- Toxicology
Background:
- Oltipraz (RP 35972) is a synthetic dithiolethione with antischistosomal history.
- Dithiolethiones in cruciferous vegetables are linked to cancer inhibition.
- Oltipraz induces Phase II detoxification enzymes, notably glutathione-S-transferase (GST).
Purpose of the Study:
- To evaluate oltipraz's chemopreventive potential against carcinogens.
- To assess oltipraz's efficacy in animal cancer models.
- To determine the maximum tolerated dose and toxicity profile in human clinical trials.
Main Methods:
- Animal studies using aflatoxin B1 and chemical carcinogens.
- Measurement of aflatoxin-DNA adducts and biliary elimination of conjugates.
- Phase I clinical trials in patients with colon polyps and individuals at risk for breast cancer, and in normal volunteers.
Main Results:
- Oltipraz inhibited aflatoxin B1-induced liver tumors in rats.
- Reduced levels of aflatoxin-DNA adducts and increased conjugate elimination were observed.
- In humans, the maximum tolerated dose was ≤125 mg daily, with Grade I/II toxicities including photosensitivity, GI, and neurologic effects.
Conclusions:
- Oltipraz demonstrates significant chemopreventive effects in animal models.
- Human trials established a maximum tolerated dose and identified key toxicities.
- Further research may explore optimal dosing and risk-benefit profiles for oltipraz.