After intravenous administration of Dacarbazine Injection, the volume of distribution exceeds total body water content suggesting localization in some body tissue, probably the liver. Its disappearance from the plasma is biphasic with initial half-life of 19 minutes and a terminal half-life of 5 hours. In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours. The average cumulative excretion of unchanged dacarbazine in the urine is 40% of the injected dose in 6 hours. Dacarbazine is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations dacarbazine is not appreciably bound to human plasma protein.
In man, dacarbazine is extensively degraded. Besides unchanged dacarbazine, 5-aminoimidazole−4−carboxamide (AIC) is a major metabolite of dacarbazine excreted in the urine. AIC is not derived endogenously but from the injected dacarbazine, because the administration of radioactive dacarbazine labeled with 14C in the imidazole portion of the molecule (dacarbazine-2-14C) gives rise to AIC-2-14C.
Although the exact mechanism of action of Dacarbazine for Injection is not known, three hypotheses have been offered:
- inhibition of DNA synthesis by acting as a purine analog
- action as an alkylating agent
- interaction with SH groups
Dacarbazine is indicated for the treatment of patients with metastasized malignant melanoma.
Further indications for dacarbazine as part of a combination chemotherapy are:
– advanced Hodgkin’s disease,
– advanced adult soft tissue sarcomas (except mesothelioma, Kaposi sarcoma).