Allopurinol

Allopurinol
ATC Code M04AA01
Formula C5H4N4O
Molar Mass (g·mol−1) 136,11
Physical State solid
Melting Point (°C) >350
PKS Value 10.2
CAS Number 315-30-0
PUB Number 135401907
Drugbank ID DB00437
Solubility low in water

Basics

Allopurinol is a drug in the uricosteroids group and is used to lower excessive levels of uric acid in the blood. It is used specifically to prevent gout, to prevent certain types of kidney stones, and for high uric acid levels that may occur during chemotherapy. It is taken by mouth or injected into a vein.

Pharmacology

Pharmacodynamics

Allopurinol is a structural analog of the natural purine base, hypoxanthine. After ingestion, allopurinol is metabolized in the liver to its active metabolite, oxypurinol (alloxanthin), which acts as an inhibitor of the enzyme xanthine oxidase. Xanthine oxidase mediates the physiological breakdown of the purine bases adenine and guanine to uric acid. In some cases, this process may be exacerbated, such as in individuals with tumor disease or those with a family history of gout. As a result, the uric acid level in the blood rises too high and deposits of uric acid crystals form in the joints of the affected persons. Allopurinol prevents the conversion of xanthine to uric acid, which is why increased xanthine is excreted by the kidneys and the uric acid level is lowered.

Pharmacokinetics

This drug is absorbed approximately 90% from the gastrointestinal tract. The maximum plasma level usually occurs after 1.5 hours. Plasma protein binding is extremely low and can therefore be neglected. Allopurinol is rapidly metabolized to the corresponding xanthine analogue, oxipurinol (alloxanthine), which is also an inhibitor of the enzyme xanthine oxidase. Allopurinol and oxypurinol are converted to their respective ribonucleotides via the "purine salvage pathway" and excreted. Approximately 80% of orally ingested allopurinol (and metabolites) are excreted in the urine. Approximately 20% of ingested allopurinol is excreted in the feces.

Drug Interactions

The drug-drug interactions associated with the use of allopurinol are extensive.

  • Azathioprine and 6-mercaptopurine: Azathioprine is metabolized to 6-mercaptopurine, which in turn is inactivated by the action of xanthine oxidase - the target of allopurinol. Simultaneous administration of allopurinol with either of these drugs at the normal dose will result in an overdose of both drugs. Therefore, only one-fourth of the usual dose of 6-mercaptopurine or azathioprine should be given.
       
  • Didanosine: Cmax and AUC values of plasma didanosine were approximately doubled with concomitant allopurinol treatment. Therefore, concomitant use is not recommended. If concomitant use is necessary, the dose must be reduced and the patient closely monitored.

Allopurinol may also increase the activity or half-life of the following drugs, in order of severity and safety of interaction:

  • Ciclosporin
  • coumarin anticoagulants, such as warfarin
  • Vidarabine
  • Chlorpropamide
  • Phenytoin
  • Theophylline
  • Cyclophosphamide
  • Doxorubicin
  • Bleomycin
  • Procarbazine
  • Mechlorethamine

Concomitant administration of the following drugs may decrease the effectiveness of allopurinol or shorten its half-life:[9]

  • Salicylates and drugs that increase the secretion of uric acid
  • Furosemide

Concomitant administration of the following drugs may cause hypersensitivity reactions or rash:

  • Ampicillin and amoxicillin
  • diuretics, especially thiazides, especially in renal failure
  • ACE inhibitors

Toxicity

Side effects

At the beginning of taking it, symptoms may often be aggravated or gout attacks may occur. This happens due to mobilization of uric acid deposits in the joints. After that, there is effective relief from the symptoms.

Common side effects when taken by mouth are itching and rash. Common side effects when used by injection are vomiting and kidney problems. For people already taking the medication, it should continue to be taken during an acute gout attack.

It is generally considered safe to take during pregnancy. However, more research is needed on this.

Toxicological data

LD50 (mouse, oral): 78 mg-kg-1

Sources

  • Drugbank
  • PubChem
  • Aktories, Förstermann, Hofmann, Starke: Allgemeine und spezielle Pharmakologie und Toxikologie, Elsvier, 2017
Markus Falkenstätter

Markus Falkenstätter
Author

Markus Falkenstätter ist Autor zu pharmazeutischen Themen in der Medizin-Redaktion von Medikamio. Er befindet sich im letzten Semester seines Pharmaziestudiums an der Universität Wien und liebt das wissenschaftliche Arbeiten im Bereich der Naturwissenschaften.

Mag. pharm Stefanie Lehenauer

Mag. pharm Stefanie Lehenauer
Lector

Stefanie Lehenauer ist seit 2020 freie Autorin bei Medikamio und studierte Pharmazie an der Universität Wien. Sie arbeitet als Apothekerin in Wien und ihre Leidenschaft sind pflanzliche Arzneimittel und deren Wirkung.

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