title: Relative bioavailability of 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) in rats and monkeys.
abstract: 4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) is being evaluated for its anticancer activities in melanoma, breast cancer, Kaposi's sarcoma and lymphoproliferative disorders. A single oral dose of 1 g/kg of A-007 in rats resulted in prolonged and low plasma levels, typically less than 150 ng/ml for several days. Similarly, a single oral dose of 5 g/kg of A-007 in monkeys resulted in prolonged and low plasma levels, typically less than 22 ng/ml for several days. Oral bioavailability data suggests that this is not an efficient mode of drug administration and availability diminishes as one progresses from rodents to primates (relative oral bioavailability 2%); thus suggesting an alternative form of drug delivery is required in higher species. A-007 is not detected in plasma after a 0.25% gel is applied topically to the skin daily for 28 days. Early clinical support the topical use of A-007 to treat cutaneous metastasis for human breast cancer. The present data further support a dermal approach for the use of A-007 to treat metastatic cutaneous cancers.
authors.affiliation: DEKK-TEC Inc., New Orleans, LO 70119, USA.
authors.forename: S
authors.initials: S
authors.lastname: Subramasnian
authors.forename: A H
authors.initials: AH
authors.lastname: Rodgers
authors.forename: L R
authors.initials: LR
authors.lastname: Morgan
authors.forename: K
authors.initials: K
authors.lastname: Soike
authors.forename: M
authors.initials: M
authors.lastname: Ratteree
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007271:Injections, Intradermal; D008297:Male; D010636:Phenols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C097674:4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone; D000970:Antineoplastic Agents; D006835:Hydrazones; D010636:Phenols