Details
Stereochemistry | ACHIRAL |
Molecular Formula | C5H4N4O |
Molecular Weight | 136.1115 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O=C1N=CNC2=C1C=NN2
InChI
InChIKey=OFCNXPDARWKPPY-UHFFFAOYSA-N
InChI=1S/C5H4N4O/c10-5-3-1-8-9-4(3)6-2-7-5/h1-2H,(H2,6,7,8,9,10)
DescriptionCurator's Comment: description was created based on several sources, including
https://www.drugs.com/allopurinol.html | https://www.ncbi.nlm.nih.gov/pubmed/11137320 | http://pubs.acs.org/doi/abs/10.1021/ja01585a023 | https://www.ncbi.nlm.nih.gov/pubmed/16507884
Curator's Comment: description was created based on several sources, including
https://www.drugs.com/allopurinol.html | https://www.ncbi.nlm.nih.gov/pubmed/11137320 | http://pubs.acs.org/doi/abs/10.1021/ja01585a023 | https://www.ncbi.nlm.nih.gov/pubmed/16507884
Allopurinol is a xanthine oxidase inhibitor used to decrease high blood uric acid levels. Allopurinol is specifically used to prevent gout, prevent specific types of kidney stones, and for the high uric acid levels that can occur with chemotherapy. Allopurinol acts on purine catabolism, without disrupting the biosynthesis of purines. It reduces the production of uric acid by inhibiting the biochemical reactions immediately preceding its formation. Allopurinol is a structural analog of the natural purine base, hypoxanthine. It is an inhibitor of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and of xanthine to uric acid, the end product of purine metabolism in man. Allopurinol is metabolized to the corresponding xanthine analog, oxypurinol (Allopurinol), which also is an inhibitor of xanthine oxidase. Allopurinol is taken by mouth or injected into a vein. Common side effects, when used by mouth, include itchiness and rash. Common side effects when used by injection include vomiting and kidney problems.
CNS Activity
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16507884
Curator's Comment: http://pubs.acs.org/doi/abs/10.1021/ja01585a023
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1929 |
2.9 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Secondary | ZYLOPRIM Approved UseINDICATIONS & USAGE THIS IS NOT AN INNOCUOUS DRUG. IT IS NOT RECOMMENDED FOR THE TREATMENT OF ASYMPTOMATIC HYPERURICEMIA. Allopurinol tablets reduce serum and urinary uric acid concentrations. Its use should be individualized for each patient and requires an understanding of its mode of action and pharmacokinetics (see CLINICAL PHARMACOLOGY, CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS). Allopurinol tablets are indicated in: -the management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy). -the management of patients with leukemia, lymphoma and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels. Treatment with allopurinol tablets should be discontinued when the potential for overproduction of uric acid is no longer present. -the management of patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients. Therapy in such patients should be carefully assessed initially and reassessed periodically to determine in each case that treatment is beneficial and that the benefits outweigh the risks. Launch Date1966 |
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Secondary | ZYLOPRIM Approved UseINDICATIONS & USAGE THIS IS NOT AN INNOCUOUS DRUG. IT IS NOT RECOMMENDED FOR THE TREATMENT OF ASYMPTOMATIC HYPERURICEMIA. Allopurinol tablets reduce serum and urinary uric acid concentrations. Its use should be individualized for each patient and requires an understanding of its mode of action and pharmacokinetics (see CLINICAL PHARMACOLOGY, CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS). Allopurinol tablets are indicated in: -the management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy). -the management of patients with leukemia, lymphoma and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels. Treatment with allopurinol tablets should be discontinued when the potential for overproduction of uric acid is no longer present. -the management of patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients. Therapy in such patients should be carefully assessed initially and reassessed periodically to determine in each case that treatment is beneficial and that the benefits outweigh the risks. Launch Date1966 |
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Primary | ZYLOPRIM Approved UseINDICATIONS & USAGE THIS IS NOT AN INNOCUOUS DRUG. IT IS NOT RECOMMENDED FOR THE TREATMENT OF ASYMPTOMATIC HYPERURICEMIA. Allopurinol tablets reduce serum and urinary uric acid concentrations. Its use should be individualized for each patient and requires an understanding of its mode of action and pharmacokinetics (see CLINICAL PHARMACOLOGY, CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS). Allopurinol tablets are indicated in: -the management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy). -the management of patients with leukemia, lymphoma and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels. Treatment with allopurinol tablets should be discontinued when the potential for overproduction of uric acid is no longer present. -the management of patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients. Therapy in such patients should be carefully assessed initially and reassessed periodically to determine in each case that treatment is beneficial and that the benefits outweigh the risks. Launch Date1966 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.64 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10583019 |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ALLOPURINOL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
3 μg/mL |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
ALLOPURINOL plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4.46 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10583019 |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ALLOPURINOL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2 h |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
ALLOPURINOL plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: Page: p.1544 |
unhealthy, 52±12 n = 268 Health Status: unhealthy Condition: Hyperuricemia| Gout Age Group: 52±12 Sex: M+F Population Size: 268 Sources: Page: p.1544 |
Disc. AE: Hypertension, Muscle cramps... AEs leading to discontinuation/dose reduction: Hypertension (1%) Sources: Page: p.1544Muscle cramps (0.37%) |
300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: Page: p.1545 |
unhealthy, 52±12 n = 268 Health Status: unhealthy Condition: Hyperuricemia| Gout Age Group: 52±12 Sex: M+F Population Size: 268 Sources: Page: p.1545 |
Disc. AE: Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea (0.37%) Sources: Page: p.1545 |
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: Page: p.2031 |
unhealthy, 53.4±8.6 n = 54 Health Status: unhealthy Condition: Gout Age Group: 53.4±8.6 Sex: M+F Population Size: 54 Sources: Page: p.2031 |
Disc. AE: Eosinophilia, Diarrhea... AEs leading to discontinuation/dose reduction: Eosinophilia (1.9%) Sources: Page: p.2031Diarrhea (1.9%) Vomiting (1.9%) |
335.7 mg 1 times / day multiple, oral (mean) Recommended Dose: 335.7 mg, 1 times / day Route: oral Route: multiple Dose: 335.7 mg, 1 times / day Sources: Page: p.417 |
unhealthy, 58.7 n = 83 Health Status: unhealthy Condition: Chronic gout Age Group: 58.7 Sex: M+F Population Size: 83 Sources: Page: p.417 |
Disc. AE: Rash... AEs leading to discontinuation/dose reduction: Rash (2.4%) Sources: Page: p.417 |
300 mg 1 times / day steady, oral (max) Dose: 300 mg, 1 times / day Route: oral Route: steady Dose: 300 mg, 1 times / day Sources: |
unhealthy n = 268 Health Status: unhealthy Condition: Gout Population Size: 268 Sources: |
Other AEs: Upper respiratory tract infections... Other AEs: Upper respiratory tract infections (below serious, 52 patients) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Muscle cramps | 0.37% Disc. AE |
300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: Page: p.1544 |
unhealthy, 52±12 n = 268 Health Status: unhealthy Condition: Hyperuricemia| Gout Age Group: 52±12 Sex: M+F Population Size: 268 Sources: Page: p.1544 |
Hypertension | 1% Disc. AE |
300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: Page: p.1544 |
unhealthy, 52±12 n = 268 Health Status: unhealthy Condition: Hyperuricemia| Gout Age Group: 52±12 Sex: M+F Population Size: 268 Sources: Page: p.1544 |
Diarrhea | 0.37% Disc. AE |
300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: Page: p.1545 |
unhealthy, 52±12 n = 268 Health Status: unhealthy Condition: Hyperuricemia| Gout Age Group: 52±12 Sex: M+F Population Size: 268 Sources: Page: p.1545 |
Diarrhea | 1.9% Disc. AE |
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: Page: p.2031 |
unhealthy, 53.4±8.6 n = 54 Health Status: unhealthy Condition: Gout Age Group: 53.4±8.6 Sex: M+F Population Size: 54 Sources: Page: p.2031 |
Eosinophilia | 1.9% Disc. AE |
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: Page: p.2031 |
unhealthy, 53.4±8.6 n = 54 Health Status: unhealthy Condition: Gout Age Group: 53.4±8.6 Sex: M+F Population Size: 54 Sources: Page: p.2031 |
Vomiting | 1.9% Disc. AE |
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: Page: p.2031 |
unhealthy, 53.4±8.6 n = 54 Health Status: unhealthy Condition: Gout Age Group: 53.4±8.6 Sex: M+F Population Size: 54 Sources: Page: p.2031 |
Rash | 2.4% Disc. AE |
335.7 mg 1 times / day multiple, oral (mean) Recommended Dose: 335.7 mg, 1 times / day Route: oral Route: multiple Dose: 335.7 mg, 1 times / day Sources: Page: p.417 |
unhealthy, 58.7 n = 83 Health Status: unhealthy Condition: Chronic gout Age Group: 58.7 Sex: M+F Population Size: 83 Sources: Page: p.417 |
Upper respiratory tract infections | below serious, 52 patients | 300 mg 1 times / day steady, oral (max) Dose: 300 mg, 1 times / day Route: oral Route: steady Dose: 300 mg, 1 times / day Sources: |
unhealthy n = 268 Health Status: unhealthy Condition: Gout Population Size: 268 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
likely | no (co-administration study) Comment: allopurinol in vivo on probes of CYP2C9, CYP2C19 and CYP2D6 metabolism suggest that there are no clinically relevant drug-drug interactions between the drugs metabolized by these enzymes and allopurinol when used concomitantly Sources: https://pubmed.ncbi.nlm.nih.gov/23802435/ |
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Sources: https://pubmed.ncbi.nlm.nih.gov/23802435/ |
no | no (co-administration study) Comment: allopurinol in vivo on probes of CYP2C9, CYP2C19 and CYP2D6 metabolism suggest that there are no clinically relevant drug-drug interactions between the drugs metabolized by these enzymes and allopurinol when used concomitantly Sources: https://pubmed.ncbi.nlm.nih.gov/23802435/ |
||
no | no (co-administration study) Comment: allopurinol in vivo on probes of CYP2C9, CYP2C19 and CYP2D6 metabolism suggest that there are no clinically relevant drug-drug interactions between the drugs metabolized by these enzymes and allopurinol when used concomitantly Sources: https://pubmed.ncbi.nlm.nih.gov/23802435/ |
|||
Sources: https://pubmed.ncbi.nlm.nih.gov/23802435/ |
no | no (co-administration study) Comment: allopurinol in vivo on probes of CYP2C9, CYP2C19 and CYP2D6 metabolism suggest that there are no clinically relevant drug-drug interactions between the drugs metabolized by these enzymes and allopurinol when used concomitantly Sources: https://pubmed.ncbi.nlm.nih.gov/23802435/ |
||
no | no (co-administration study) Comment: allopurinol in vivo on probes of CYP2C9, CYP2C19 and CYP2D6 metabolism suggest that there are no clinically relevant drug-drug interactions between the drugs metabolized by these enzymes and allopurinol when used concomitantly Sources: https://pubmed.ncbi.nlm.nih.gov/23802435/ |
|||
Sources: https://pubmed.ncbi.nlm.nih.gov/23802435/ |
no | no (co-administration study) Comment: allopurinol in vivo on probes of CYP2C9, CYP2C19 and CYP2D6 metabolism suggest that there are no clinically relevant drug-drug interactions between the drugs metabolized by these enzymes and allopurinol when used concomitantly Sources: https://pubmed.ncbi.nlm.nih.gov/23802435/ |
||
no | no (co-administration study) Comment: allopurinol in vivo on probes of CYP2C9, CYP2C19 and CYP2D6 metabolism suggest that there are no clinically relevant drug-drug interactions between the drugs metabolized by these enzymes and allopurinol when used concomitantly Sources: https://pubmed.ncbi.nlm.nih.gov/23802435/ |
PubMed
Title | Date | PubMed |
---|---|---|
Clinical, serologic, and parasitologic follow-up after long-term allopurinol therapy of dogs naturally infected with Leishmania infantum. | 1999 Jul-Aug |
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Rasburicase. | 2001 |
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Effect of antioxidants on L-glutamate and N-methyl-4-phenylpyridinium ion induced-neurotoxicity in PC12 cells. | 2001 Apr |
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Bioequivalence of allopurinol and its metabolite oxipurinol in two tablet formulations. | 2001 Apr |
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Successful treatment of visceral leishmaniasis with allopurinol plus ketoconazole in an infant who developed pancreatitis caused by meglumine antimoniate. | 2001 Apr |
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Photoreactivation of alloxanthine-inhibited xanthine oxidase. | 2001 Apr |
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Increased cGMP phosphodiesterase activity mediates renal resistance to ANP in rats with bile duct ligation. | 2001 Apr |
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Hepatic artery resistance as a marker for preservation/reperfusion injury. | 2001 Feb-Mar |
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Effect of sodium lactobionate sucrose solution on the function of liver grafts from non-heart-beating pig donors. | 2001 Feb-Mar |
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Efficacy and safety of desensitization to allopurinol following cutaneous reactions. | 2001 Jan |
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The multidrug resistance protein MRP1 mediates the release of glutathione disulfide from rat astrocytes during oxidative stress. | 2001 Jan |
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Allopurinol neurocardiac protection trial in infants undergoing heart surgery using deep hypothermic circulatory arrest. | 2001 Jul |
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A randomised, blinded, placebo-controlled clinical trial with allopurinol in canine leishmaniosis. | 2001 Jul 27 |
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Clinical impact of histidine-ketoglutarate-tryptophan (HTK) cardioplegic solution on the perioperative period in open heart surgery patients. | 2001 Jul-Aug |
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Accelerated tissue aging and increased oxidative stress in broiler chickens fed allopurinol. | 2001 Jun |
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Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-alpha is mediated by ceramide. | 2001 Jun |
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Cardioprotective effect of propranolol from alcohol-induced heart muscle damage as assessed by plasma cardiac troponin-t. | 2001 Jun |
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An evaluation of the mutagenicity, metabolism, and DNA adduct formation of 5-nitrobenzo[b]naphtho[2,1-d]thiophene. | 2001 Jun |
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Eicosanoids and delayed graft function in human renal transplantation. | 2001 Jun |
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Elevated Fas-expression and cell death but normal TUNEL detection in experimental liver preservation from non-heart-beating donors. | 2001 Jun |
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Improvement of postpreservation viability of livers from non-heart-beating donors by fibrinolytic preflush with streptokinase upon graft retrieval. | 2001 Jun |
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Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent attacks of gout? | 2001 Mar |
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Prevention of nephrolithiasis. | 2001 Mar |
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Elevated superoxide production by active H-ras enhances human lung WI-38VA-13 cell proliferation, migration and resistance to TNF-alpha. | 2001 Mar 22 |
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Adenine phosphoribosyltransferase deficiency and renal allograft dysfunction. | 2001 May |
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Induction of oxidative stress by humic acid through increasing intracellular iron: a possible mechanism leading to atherothrombotic vascular disorder in blackfoot disease. | 2001 May 18 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/pro/allopurinol.html
The dosage of Allopurinol to accomplish full control of gout and to lower serum uric acid to normal or near-normal levels varies with the severity of the disease. The average is 200 to 300 mg per day for patients with mild gout and 400 to 600 mg per day for those with moderately severe tophaceous gout. The appropriate dosage may be administered in divided doses or as a single equivalent dose with the 300 mg tablet. Dosage requirements in excess of 300 mg should be administered in divided doses. The minimal effective dosage is 100 to 200 mg daily and the maximal recommended dosage is 800 mg daily.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26968635
Primary rat osteoblast cells were obtained from 2-day-old neonatal Sprague-Dawley rats. Following isolation, cells were resuspended in Dulbecco's Modified Essential Medium, supplemented with 10% foetal calf serum (FCS), 2 mM L-glutamine, 100 U/ml penicillin, 100 mg/ml streptomycin and 0.25 mg/ml amphotericin (complete mixture abbreviated to DMEM). Cells were cultured for 2–4 days in a humidified atmosphere of 5% CO2–95% air at 37 °C in 75 cm2 flasks until confluent. Upon confluence, cells were sub-cultured into 24- well trays in DMEM supplemented with 2 mM β-glycerophosphate, 50 μg/ml ascorbic acid and 10 nM dexamethasone (supplemented DMEM), with half medium changes every 3 days. Osteoblasts were cultured in the presence of allopurinol and oxypurinol (1 nM–10 mM) to determine the effect on cell proliferation, differentiation, function and gene expression. For the bone formation experiments, cells were also treated with febuxostat and, as a positive control of an anabolic agent, BMP2 (0.1 mM). Unless stated, experiments were carried out at 2 time points during the osteoblast culture; day 7, which represents differentiating osteoblasts, and day 14 (mature, bone forming osteoblasts). All experiments were carefully pH-controlled because bone mineralisation is extremely sensitive to inhibition by acidosis
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NCI_THESAURUS |
C1637
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WHO-VATC |
QM04AA51
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WHO-ESSENTIAL MEDICINES LIST |
8.2
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NCI_THESAURUS |
C921
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QM04AA01
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LIVERTOX |
NBK548098
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M04AA51
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M04AA01
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NDF-RT |
N0000000206
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N0000175698
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WHO-ESSENTIAL MEDICINES LIST |
2.3
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184856-42-6
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63CZ7GJN5I
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Allopurinol
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m1541
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39464-14-7
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22767-92-6
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101655
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ALLOPURINOL
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ALLOPURINOL
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PRIMARY | Description: A white or almost white, microcrystalline powder; odourless or almost odourless. Solubility: Very slightly soluble in water and in ethanol (~750 g/l) TS and ether R. Category: Xanthine oxidase inhibitor. Storage: Allopurinol should be kept in a well-closed container. Definition: Allopurinol contains not less than 98.0% and not more than 101.0% of C5H4N4O, calculated with reference to the dried substance. | ||
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1013002
Created by
admin on Sat Dec 16 18:03:23 GMT 2023 , Edited by admin on Sat Dec 16 18:03:23 GMT 2023
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1731
Created by
admin on Sat Dec 16 18:03:23 GMT 2023 , Edited by admin on Sat Dec 16 18:03:23 GMT 2023
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D000493
Created by
admin on Sat Dec 16 18:03:23 GMT 2023 , Edited by admin on Sat Dec 16 18:03:23 GMT 2023
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DTXSID4022573
Created by
admin on Sat Dec 16 18:03:23 GMT 2023 , Edited by admin on Sat Dec 16 18:03:23 GMT 2023
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DB00437
Created by
admin on Sat Dec 16 18:03:23 GMT 2023 , Edited by admin on Sat Dec 16 18:03:23 GMT 2023
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ACTIVE MOIETY
METABOLITE ACTIVE (PARENT)
SALT/SOLVATE (PARENT)