Relative bioavailability of 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) in rats and monkeys

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.