Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C5H5N5S |
| Molecular Weight | 167.192 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
NC1=NC2=C(N=CN2)C(=S)N1
InChI
InChIKey=WYWHKKSPHMUBEB-UHFFFAOYSA-N
InChI=1S/C5H5N5S/c6-5-9-3-2(4(11)10-5)7-1-8-3/h1H,(H4,6,7,8,9,10,11)
| Molecular Formula | C5H5N5S |
| Molecular Weight | 167.192 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionSources: http://www.drugbank.ca/drugs/DB00352Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/12429slr021_tabloid_lbl.pdf
Sources: http://www.drugbank.ca/drugs/DB00352
Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/12429slr021_tabloid_lbl.pdf
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). 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. Thioguanine is used for remission induction and remission consolidation treatment of acute nonlymphocytic leukemias. It is marketed under the trade name Lanvis and Tabloid among others.
CNS Activity
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: DNA Sources: http://www.drugbank.ca/drugs/DB00352 |
|||
Target ID: CHEMBL614844 |
20.0 µM [IC50] | ||
Target ID: CHEMBL2111369 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | TABLOID Approved UseIndications and Usage for Thioguanine
a) Acute Nonlymphocytic Leukemias
TABLOID brand Thioguanine is indicated for remission induction and remission consolidation treatment of acute nonlymphocytic leukemias. However, it is not recommended for use during maintenance therapy or similar long-term continuous treatments due to the high risk of liver toxicity.
The response to this agent depends upon the age of the patient (younger patients faring better than older) and whether Thioguanine is used in previously treated or previously untreated patients. Reliance upon Thioguanine alone is seldom justified for initial remission induction of acute nonlymphocytic leukemias because combination chemotherapy including Thioguanine results in more frequent remission induction and longer duration of remission than Thioguanine alone.
b) Other Neoplasms
TABLOID brand Thioguanine is not effective in chronic lymphocytic leukemia, Hodgkin’s lymphoma, multiple myeloma, or solid tumors. Although Thioguanine is one of several agents with activity in the treatment of the chronic phase of chronic myelogenous leukemia, more objective responses are observed with MYLERAN® (busulfan), and therefore busulfan is usually regarded as the preferred drug. Launch Date1966 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
313 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11422012 |
40 mg/m² 1 times / day multiple, oral dose: 40 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: |
THIOGUANINE plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
586 pmol × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11422012 |
40 mg/m² 1 times / day multiple, oral dose: 40 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: |
THIOGUANINE plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
4.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27463047 |
40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
THIOGUANINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
Doses
| Dose | Population | Adverse events |
|---|---|---|
20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Other AEs: Pain, Nausea and vomiting... Other AEs: Pain (grade 1-2, 9.6%) Sources: Nausea and vomiting (grade 1-2, 20%) Leukopenia (grade 1-2, 11.8%) Thrombocytopenia (grade 1-3, 3.7%) Hepatotoxicity (grade 1-2, 24.4%) Headache (grade 1-2, 8.9%) Anemia (grade 1-3, 8.9%) Gamma-glutamyltransferase increased (grade 1-4, 16.3%) Diarrhea (grade 2, 1.4%) Skin toxicity (grade 1-2, 11.8%) Hair loss (grade 1, 5.2%) Infection (grade 1-3, 26.7%) Blood urea nitrogen increased (grade 1, 1.4%) Neurotoxicity (grade 1-2, 1.4%) Hemorrhage (grade 3, 0.7%) Stomatitis (grade 1, 0.7%) Creatinine increased (grade 2, 0.7%) Cardiac arrhythmias (grade 1, 0.7%) Constipation (grade 1, 0.7%) |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
Disc. AE: Pain, Nausea and vomiting... AEs leading to discontinuation/dose reduction: Pain (grade 1-3, 6.1%) Sources: Nausea and vomiting (grade 1-2, 4.4%) Leukopenia (grade 1-3, 2.7%) Thrombocytopenia (grade 1-3, 2.7%) Hepatotoxicity (grade 1-2, 2.4%) Headache (grade 1-2, 1.7%) Anemia (grade 1-4, 0.7%) Gamma-glutamyltransferase increased (grade 2-3, 1%) Diarrhea (grade 2-4, 1%) Skin toxicity (grade 1, 0.7%) Hair loss (grade 1, 0.7%) Cardiac dysfunction (grade 3, 0.3%) Pericarditis (grade 2, 0.3%) |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
Disc. AE: Pancreatitis, Headache... Other AEs: Headache, Nausea... AEs leading to discontinuation/dose reduction: Pancreatitis (2.7%) Other AEs:Headache (5.4%) Pneumonia (2.7%) Leucopenia (5.4%) Headache (45.9%) Sources: Nausea (27%) Vomiting (5.4%) Pruritus (8.1%) Arthralgia (8.1%) Alopecia (8.1%) Dysaesthesia (2.7%) Eczema (10.8%) Exanthema (5.4%) Photosensitivity allergic reac (5.4%) Erythema nodosum (2.7%) Rotavirus infection (2.7%) Respiratory tract infections (29.7%) Urinary tract infections (10.8%) Genital candidiasis (5.4%) Herpes labialis (2.7%) Transaminases increased (5.4%) Leucopenia (8.1%) Anaemia (2.7%) Thrombopenia (2.7%) |
1200 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 1200 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 1200 mg/m2, 1 times / 3 weeks Sources: |
unhealthy, 37-70 years Health Status: unhealthy Age Group: 37-70 years Sex: M+F Sources: |
Disc. AE: Creatinine increased... Other AEs: Leukopenia... AEs leading to discontinuation/dose reduction: Creatinine increased (25%) Other AEs:Leukopenia (25%) Sources: |
300 mg/m2 1 times / week multiple, intravenous MTD Dose: 300 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 300 mg/m2, 1 times / week Sources: |
unhealthy, Patients < 21 years Health Status: unhealthy Age Group: Patients < 21 years Sources: |
Other AEs: Neutropenia, Anemia... Other AEs: Neutropenia (grade 3, 16.1%) Sources: Anemia (grade 3, 16.1%) Thrombocytopenia (grade 3, 16.1%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Cardiac arrhythmias | grade 1, 0.7% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Constipation | grade 1, 0.7% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Stomatitis | grade 1, 0.7% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Blood urea nitrogen increased | grade 1, 1.4% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Hair loss | grade 1, 5.2% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Neurotoxicity | grade 1-2, 1.4% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Leukopenia | grade 1-2, 11.8% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Skin toxicity | grade 1-2, 11.8% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Nausea and vomiting | grade 1-2, 20% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Hepatotoxicity | grade 1-2, 24.4% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Headache | grade 1-2, 8.9% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Pain | grade 1-2, 9.6% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Infection | grade 1-3, 26.7% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Thrombocytopenia | grade 1-3, 3.7% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Anemia | grade 1-3, 8.9% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Gamma-glutamyltransferase increased | grade 1-4, 16.3% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Creatinine increased | grade 2, 0.7% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Diarrhea | grade 2, 1.4% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Hemorrhage | grade 3, 0.7% | 20 mg 1 times / day multiple, oral Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Hair loss | grade 1, 0.7% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Skin toxicity | grade 1, 0.7% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Headache | grade 1-2, 1.7% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Hepatotoxicity | grade 1-2, 2.4% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Nausea and vomiting | grade 1-2, 4.4% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Leukopenia | grade 1-3, 2.7% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Thrombocytopenia | grade 1-3, 2.7% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Pain | grade 1-3, 6.1% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Anemia | grade 1-4, 0.7% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Pericarditis | grade 2, 0.3% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Gamma-glutamyltransferase increased | grade 2-3, 1% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Diarrhea | grade 2-4, 1% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Cardiac dysfunction | grade 3, 0.3% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 16–82 years Health Status: unhealthy Age Group: 16–82 years Sex: M+F Sources: |
| Eczema | 10.8% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Urinary tract infections | 10.8% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Anaemia | 2.7% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Dysaesthesia | 2.7% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Erythema nodosum | 2.7% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Herpes labialis | 2.7% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Rotavirus infection | 2.7% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Thrombopenia | 2.7% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Pancreatitis | 2.7% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Pneumonia | 2.7% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Nausea | 27% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Respiratory tract infections | 29.7% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Headache | 45.9% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Exanthema | 5.4% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Genital candidiasis | 5.4% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Photosensitivity allergic reac | 5.4% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Transaminases increased | 5.4% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Vomiting | 5.4% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Headache | 5.4% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Leucopenia | 5.4% Disc. AE |
40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Alopecia | 8.1% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Arthralgia | 8.1% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Leucopenia | 8.1% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Pruritus | 8.1% | 40 mg 1 times / day multiple, oral Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: |
unhealthy, 22–61 years Health Status: unhealthy Age Group: 22–61 years Sex: M+F Sources: |
| Leukopenia | 25% | 1200 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 1200 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 1200 mg/m2, 1 times / 3 weeks Sources: |
unhealthy, 37-70 years Health Status: unhealthy Age Group: 37-70 years Sex: M+F Sources: |
| Creatinine increased | 25% Disc. AE |
1200 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 1200 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 1200 mg/m2, 1 times / 3 weeks Sources: |
unhealthy, 37-70 years Health Status: unhealthy Age Group: 37-70 years Sex: M+F Sources: |
| Anemia | grade 3, 16.1% | 300 mg/m2 1 times / week multiple, intravenous MTD Dose: 300 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 300 mg/m2, 1 times / week Sources: |
unhealthy, Patients < 21 years Health Status: unhealthy Age Group: Patients < 21 years Sources: |
| Neutropenia | grade 3, 16.1% | 300 mg/m2 1 times / week multiple, intravenous MTD Dose: 300 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 300 mg/m2, 1 times / week Sources: |
unhealthy, Patients < 21 years Health Status: unhealthy Age Group: Patients < 21 years Sources: |
| Thrombocytopenia | grade 3, 16.1% | 300 mg/m2 1 times / week multiple, intravenous MTD Dose: 300 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 300 mg/m2, 1 times / week Sources: |
unhealthy, Patients < 21 years Health Status: unhealthy Age Group: Patients < 21 years Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 4.0 |
no | |||
Page: 4.0 |
no | |||
Page: 4.0 |
weak |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 1.0 |
major | |||
Page: 1.0 |
minor | |||
| yes | yes (pharmacogenomic study) Comment: patients with reduced TPMT receiving usual doses of mercaptopurine, accumulate excessive cellular concentrations of active 6-TGNs Page: 3.0 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Implication of protein kinase C in the regulation of DNA mismatch repair protein expression and function. | 2002-05-17 |
|
| Photodynamic therapy of DNA mismatch repair-deficient and -proficient tumour cells. | 2002-04-08 |
|
| Novel glutathione-dependent thiopurine prodrugs: evidence for enhanced cytotoxicity in tumor cells and for decreased bone marrow toxicity in mice. | 2002-04 |
|
| X-ray induced mutation in Syrian hamster fetal cells. | 2002-03-20 |
|
| Childhood hyperuricemia and acute renal failure resulting from a missense mutation in the HPRT gene. | 2002-03-15 |
|
| Pharmacological characterization of the ATP-dependent low K(m) guanosine 3',5'-cyclic monophosphate (cGMP) transporter in human erythrocytes. | 2002-03-01 |
|
| [Hypomethylation and multiple sclerosis, the susceptibility factor?]. | 2002-03 |
|
| Aphidicolin induces 6-thioguanine resistant mutants in human diploid fibroblasts. | 2002-02-20 |
|
| Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues. | 2002-02-01 |
|
| Specific [(3)H]-guanosine binding sites in rat brain membranes. | 2002-02 |
|
| Diversity of the apoptotic response to chemotherapy in childhood leukemia. | 2002-02 |
|
| Effect of methotrexate polyglutamates on thioguanine nucleotide concentrations during continuation therapy of acute lymphoblastic leukemia with mercaptopurine. | 2002-02 |
|
| Flow cytometric determination of HPRT-variants in human peripheral blood lymphocytes. | 2002-01-29 |
|
| Genetic toxicology studies with glutaraldehyde. | 2002-01-25 |
|
| Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome. | 2002-01-01 |
|
| Frequent detection of T cells with mutations of the hypoxanthine-guanine phosphoribosyl transferase gene in patients with paroxysmal nocturnal hemoglobinuria. | 2002-01-01 |
|
| The thiopurine S-methyltransferase gene locus -- implications for clinical pharmacogenomics. | 2002-01 |
|
| Inflammatory bowel disease. | 2002-01 |
|
| HPLC determination of thiopurine nucleosides and nucleotides in vivo in lymphoblasts following mercaptopurine therapy. | 2002-01 |
|
| Continuing therapy for childhood acute lymphoblastic leukaemia: clinical and cellular pharmacology of methotrexate, 6-mercaptopurine and 6-thioguanine. | 2001-12 |
|
| Renal cell carcinoma as a secondary malignancy after treatment of acute promyelocytic leukemia. | 2001-12 |
|
| Toxoplasma gondii: mechanism of the parasitostatic action of 6-thioxanthine. | 2001-12 |
|
| Why measure thiopurine methyltransferase activity? Direct administration of 6-thioguanine might be the alternative for 6-mercaptopurine or azathioprine. | 2001-12 |
|
| Mechanisms of tolerance to DNA damaging therapeutic drugs. | 2001-12 |
|
| Comparative pharmacokinetics of oral 6-mercaptopurine and intravenous 6-mercaptopurine riboside in children. | 2001-12 |
|
| Loss of DNA mismatch repair imparts defective cdc2 signaling and G(2) arrest responses without altering survival after ionizing radiation. | 2001-11-15 |
|
| Substitution F569S converts UapA, a specific uric acid-xanthine transporter, into a broad specificity transporter for purine-related solutes. | 2001-11-02 |
|
| The mouse guanylate kinase double mutant E72Q/D103N is a functional adenylate kinase. | 2001-11 |
|
| Review article: the treatment of inflammatory bowel disease with 6-mercaptopurine or azathioprine. | 2001-11 |
|
| Possible implication of thiopurine S-methyltransferase in occurrence of infectious episodes during maintenance therapy for childhood lymphoblastic leukemia with mercaptopurine. | 2001-11 |
|
| Treatment of psoriasis. Part 2. Systemic therapies. | 2001-11 |
|
| Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide. | 2001-11 |
|
| Hypoxia-induced enrichment and mutagenesis of cells that have lost DNA mismatch repair. | 2001-10-15 |
|
| FAB M4 and high CD14 surface expression is associated with high cellular resistance to Ara-C and daunorubicin: implications for clinical outcome in acute myeloid leukaemia. | 2001-10 |
|
| Managing the glucocorticoid dependent inflammatory bowel disease patient. | 2001-10 |
|
| Acute arterial occlusion as the presenting feature in acute promyelocytic leukaemia. | 2001-10 |
|
| Co-amplification of dhfr and a homologue of hmsh3 in a Chinese hamster methotrexate-resistant cell line correlates with resistance to a range of chemotherapeutic drugs. | 2001-10 |
|
| 6-mercaptopurine metabolite levels in children with inflammatory bowel disease. | 2001-10 |
|
| Targeting DNA mismatch repair for radiosensitization. | 2001-10 |
|
| Determination of thiopurine methyltransferase activity in human erythrocytes by high-performance liquid chromatography: comparison with the radiochemical method. | 2001-10 |
|
| Suppression of spontaneous and hydrogen peroxide-induced mutagenesis by the antioxidant ascorbate in mismatch repair-deficient human colon cancer cells. | 2001-10 |
|
| Intensive timed sequential remission induction chemotherapy with high-dose cytarabine for childhood acute myeloid leukemia. | 2001-10 |
|
| Enhanced expression and activity of DNA polymerase beta in human ovarian tumor cells: impact on sensitivity towards antitumor agents. | 2001-09-27 |
|
| Remission induction therapy: the more intensive the better? | 2001-08 |
|
| Reversal of cytosine arabinoside (ara-C) resistance by the synergistic combination of 6-thioguanine plus ara-C plus PEG-asparaginase (TGAP) in human leukemia lines lacking or expressing p53 protein. | 2001-08 |
|
| Recent advances in the pharmacogenomics of thiopurine methyltransferase. | 2001 |
|
| Generation of single-copy transgenic mouse embryos directly from ES cells by tetraploid embryo complementation. | 2001 |
|
| Favorable outcome for children and adolescents with T-cell lymphoblastic lymphoma with an intensive ALL-type therapy without local radiotherapy. | 2001 |
|
| Pharmacogenetics: the therapeutic drug monitoring of the future? | 2001 |
|
| Pharmacokinetic considerations in the treatment of inflammatory bowel disease. | 2001 |
Sample Use Guides
Single Agent Chemotherapy: Usual Initial dose: 2 mg/kg/day orally.
If, after 4 weeks on this dosage, there is no clinical improvement and no leukocyte or platelet depression, the dosage may be cautiously increased to 3 mg/kg per day. The total daily dose may be given at one time.
As a part of combination therapy for induction of remission in patients with acute nonlymphocytic leukemia: 75 to 200 mg/m2/day in 1 to 2 divided doses for 5 to 7 days or until remission is attained.
Route of Administration:
Oral
| Substance Class |
Chemical
Created
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on
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WIX31ZPX66
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Validated (UNII)
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N0000180853
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C1556
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QL01BB03
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m10760
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SOLVATE->ANHYDROUS |
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SALT/SOLVATE -> PARENT |
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METABOLIC ENZYME -> SUBSTRATE |
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METABOLIC ENZYME -> SUBSTRATE |
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TARGET -> INHIBITOR |
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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METABOLITE INACTIVE -> PARENT |
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METABOLITE ACTIVE -> PRODRUG |
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| Related Record | Type | Details | ||
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ACTIVE MOIETY |
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