化合物信息

Drug Groups

approved

Description

An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)

Indication

For the treatment of metastatic malignant melanoma. In addition, dacarbazine is also indicated for Hodgkin's disease as a secondary-line therapy when used in combination with other antineoplastic agents.

Pharmacology

Dacarbazine is a synthetic analog of naturally occurring purine precursor 5-amino-1H-imidazole-4-carboxamide (AIC). After intravenous administration of dacarbazine, 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 DTIC in the urine is 40% of the injected dose in 6 hours. 1 DTIC is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations dacarbazine is not appreciably bound to human plasma protein.

Toxicity

LD₅₀=350mg/kg (orally in mice)

Affected Organisms

Biotransformation

Hepatic

Absorption

Erratic, slow and incomplete

Half Life

5 hours

Protein Binding

Less than 5%

Elimination

Dacarbazine is subject to renal tubular secretion rather than glomerular filtration. In man, dacarbazine is extensively degraded. Besides unchanged dacarbazine, 5-aminoimidazole -4 carboxamide (AIC) is a major metabolite of dacarbazine excreted in the urine.

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