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Comparative preclinical toxicology and pharmacology of 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) in vitro and in rodents and primates.

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.
AuthorsL R Morgan, A H Rodgers, D Fan, K Soike, M Ratterree, B W Sartin, T J Harrison
JournalIn vivo (Athens, Greece) (In Vivo) 1997 Jan-Feb Vol. 11 Issue 1 Pg. 29-37 ISSN: 0258-851X [Print] Greece
PMID9067770 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone
  • Antineoplastic Agents
  • Hydrazones
  • Phenols
Topics
  • Administration, Oral
  • Animals
  • Antineoplastic Agents (pharmacokinetics, toxicity)
  • Bone Marrow Cells
  • Breast Neoplasms
  • Carcinogenicity Tests
  • Chlorocebus aethiops
  • Colonic Neoplasms
  • Dose-Response Relationship, Drug
  • Eye Infections (chemically induced)
  • Female
  • Fibroblasts (cytology, drug effects)
  • Humans
  • Hydrazones (pharmacokinetics, toxicity)
  • Injections, Intraperitoneal
  • Kidney Neoplasms
  • Lung Neoplasms
  • Male
  • Melanoma
  • Mice
  • Mice, Inbred Strains
  • Phenols (pharmacokinetics, toxicity)
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Reproduction (drug effects)
  • Skin Diseases (chemically induced)
  • Tumor Cells, Cultured (drug effects)

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