Abstract
4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) is being evaluated for its anticancer activities. Acute, subacute and chronic oral, dermal, opthalmic and dermal LD50 and acceptance studies in adult mice, rats, rabbits and monkeys demonstrated some vomiting at 5 g/kg doses in monkeys but otherwise no unacceptable toxicities. In vitro, T.I. for A-007 were calculated using murine bone marrow GM-CFC and human cancer cell lines. A relative oral bioavailability factor of 2% was calculated for rats and monkeys for plasma A-007. Non-compartmental pharmacokinetic analysis suggests enterohepatic circulation. Plasma A-007 could not be detected after applying a 0.25% gel topically. Generally, A-007 is well tolerated.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Administration, Oral
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Animals
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / toxicity*
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Bone Marrow Cells
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Breast Neoplasms
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Carcinogenicity Tests
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Chlorocebus aethiops
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Colonic Neoplasms
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Dose-Response Relationship, Drug
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Eye Infections / chemically induced
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Female
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Humans
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Hydrazones / pharmacokinetics
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Hydrazones / toxicity*
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Injections, Intraperitoneal
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Kidney Neoplasms
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Lung Neoplasms
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Male
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Melanoma
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Mice
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Mice, Inbred Strains
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Phenols / pharmacokinetics
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Phenols / toxicity*
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Rabbits
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Rats
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Rats, Sprague-Dawley
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Reproduction / drug effects
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Skin Diseases / chemically induced
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Tumor Cells, Cultured / drug effects
Substances
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4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone
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Antineoplastic Agents
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Hydrazones
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Phenols