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After intravenous administration of DTlC-Dome, 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.¹ In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours.¹ The average cumulative excretion of unchanged DTlC in the urine is 40% of the injected dose in 6 hours.1 DTlC is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations DTIC is not appreciably bound to human plasma protein.

In man, DTlC is extensively degraded. Besides unchanged DTlC, 5-aminoimidazole -4 carboxamide (AlC) is a major metabolite of DTlC excreted in the urine. AlC is not derived endogenously but from the injected DTlC, because the administration of radioactive DTlC labeled with ¹⁴C in the imidazole portion of the molecule (DTlC-2-¹⁴C) gives rise to AIC-2-¹⁴C¹.

Although the exact mechanism of action of DTIC-Dome (dacarbazine) is not known, three hypotheses have been offered:

1. inhibition of DNA synthesis by acting as a purine analog
2. action as an alkylating agent
3. interaction with SH groups

REFERENCES

1. Loo, T.J., et al.: Mechanism of action and pharmacology studies with DTlC (NSC-45388). Cancer Treatment Reports 60: 149–152, 1976.

Last reviewed on RxList: 11/5/2008
This monograph has been modified to include the generic and brand name in many instances.