Tioguaninum
Tioguaninum Uses, Dosage, Side Effects, Food Interaction and all others data.
An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.
Thioguanine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Thioguanine was first synthesized and entered into clinical trial more than 30 years ago. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Thioguanine is cross-resistant with mercaptopurine. Cytotoxicity is cell cycle phase-specific (S-phase).
| Trade Name | Tioguaninum |
| Generic | Tioguanine |
| Tioguanine Other Names | 2-Amino 6MP, 6-Mercaptoguanine, 6-TG, 6-Thioguanine, Thioguanine, Tioguanin, Tioguanina, Tioguanine, Tioguaninum |
| Type | |
| Formula | C5H5N5S |
| Weight | Average: 167.192 Monoisotopic: 167.026565875 |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Tioguaninum is a purine analogue antineoplastic agent used for the induction of remission, and for remission consolidation in patients with acute nonlymphocytic anemias.
For remission induction and remission consolidation treatment of acute nonlymphocytic leukemias.
Tioguaninum is also used to associated treatment for these conditions: Acute Nonlymphocytic Leukemia, Nonlymphocytic Acute myeloid leukemia
How Tioguaninum works
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.
Toxicity
Oral, mouse: LD50 = 160 mg/kg. Symptoms of overdose include nausea, vomiting, malaise, hypotension, and diaphoresis.
Food Interaction
- Take with or without food. However, food intake may lower tioguanine serum levels.
Elimination Route
Absorption of an oral dose is incomplete and variable, averaging approximately 30% of the administered dose (range: 14% to 46%)
Half Life
When the compound was given in singles doses of 65 to 300 mg/m^2, the median plasma half-disappearance time was 80 minutes (range 25-240 minutes)
Innovators Monograph
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