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Tioguanine volume of distribution
What is Tioguanine
An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. (PubChem)
Tioguanine mechanism of action
Thioguanine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to 6-thioguanilyic acid (TGMP), which reaches high intracellular concentrations at therapeutic doses. TGMP interferes with the synthesis of guanine nucleotides by its inhibition of purine biosynthesis by pseudofeedback inhibition of glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway of purine ribonucleotide synthesis. TGMP also inhibits the conversion of inosinic acid (IMP) to xanthylic acid (XMP) by competition for the enzyme IMP dehydrogenase. Thioguanine nucleotides are incorporated into both the DNA and the RNA by phosphodiester linkages, and some studies have shown that incorporation of such false bases contributes to the cytotoxicity of thioguanine. Its tumor inhibitory properties may be due to one or more of its effects on feedback inhibition of de novo purine synthesis; inhibition of purine nucleotide interconversions; or incorporation into the DNA and RNA. The overall result of its action is a sequential blockade of the utilization and synthesis of the purine nucleotides.
Dosage forms of Tioguanine
Aspen Pharma Trading Limited
Humans and other mammals
Indication of Tioguanine
For remission induction and remission consolidation treatment of acute nonlymphocytic leukemias.
Toxicity of Tioguanine
Oral, mouse: LD sub 50 /sub = 160 mg/kg. Symptoms of overdose include nausea, vomiting, malaise, hypotension, and diaphoresis.
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