Triazenes

dacarbazine (dtic) Dacarbazine functions as a methylating agent after metabolic activation in the liver. The active form is a monomethyl triazeno metabolite, MTIC, which kills cells in all phases of the cell cycle. Resistance has been ascribed to removal of methyl groups from the O6-guanine bases in DNA by AGT. Dacarbazine is administered intravenously. After an initial rapid phase of disappearance (t1/2 ~20 minutes), dacarbazine is removed from plasma with a terminal t1/2 of ~5 hours. The t1/2 is prolonged in the presence of hepatic or renal disease. Almost 50% of the compound is excreted intact in the urine by tubular secretion. Elevated urinary concentrations of 5-aminoimidazole-4-carboxamide are derived from the catabolism of dacarbazine, rather than by inhibition of de novo purine biosynthesis. Dacarbazine (dtic-dome, others) for malignant melanoma is given in doses of 3.5 mg/kg/day, intravenously, for a 10-day period, repeated every 28 days. Alternatively, 250 mg/m2 can be given daily for 5 days and repeated every 3 weeks. Extravasation of the drug may cause tissue damage and severe pain. At present, dacarbazine is employed in combination regimens for the treatment of Hodgkin's disease. It is less effective against malignant melanoma and adult sarcomas. The toxicity of DTIC includes nausea and vomiting in >90% of patients; vomiting usually develops 1-3 hours after treatment and may last up to 12 hours. Myelosuppression, with both leukopenia and thrombocytopenia, usually is mild to moderate. A flu-like syndrome consisting of chills, fever, malaise, and myalgias may occur during DTIC treatment. Hepatotoxicity, alopecia, facial flushing, neurotoxicity, and dermatologic reactions also have been reported.

temozolomide Temozolomide (temodar) is a triazene that has significant activity in patients with malignant gliomas, where it is the standard agent in combination with radiation therapy. Temozolomide, like dacarbazine, forms the methylating metabolite MTIC and kills cells in all phases of the cell cycle. Temozolomide is administered orally and its bioavailability approaches 100%. Maximum plasma drug concentration reaches 5 ^g/mL, or ~10 ^M, 1 hour after administration of a dose of 200 mg, and declines with an elimination t1/2 of 1.2 hours. The primary active metabolite MTIC reaches a maximum plasma concentration of 150 ng/mL 90 minutes after a dose and declines with a t1/2 of 2 hours. Little intact drug is recovered in the urine, the primary urinary metabolite being the inactive imidazole carboxamide. The pharmacokinetics of temozolomide are linear over the dose range of 100-260 mg/m2. The toxicities of temozolomide mirror those of DTIC.

How To Prevent Skin Cancer

How To Prevent Skin Cancer

Complete Guide to Preventing Skin Cancer. We all know enough to fear the name, just as we do the words tumor and malignant. But apart from that, most of us know very little at all about cancer, especially skin cancer in itself. If I were to ask you to tell me about skin cancer right now, what would you say? Apart from the fact that its a cancer on the skin, that is.

Get My Free Ebook


Post a comment