Allopurinol detailed information

Allopurinol detailed information

Clinical data
Pregnancy category	C(USA)
Routes of administration	tablet (100, 300 mg)
ATC code	M04AA01 (WHO)
Legal status
Legal status	Schedule 6 (USA)
Pharmacokinetic data
Bioavailability	78±20%
Protein binding	Negligible
Metabolism	hepatic (80% oxypurinol, 10% allopurinol ribosides)
Elimination half-life	2 hours (oxypurinol 18-30 hours)
Identifiers
IUPAC name 3,5,7,8-tetrazabicyclo[4.3.0] nona-3,5,9-trien-2-one
CAS Number	315-30-0
PubChem CID	2094
DrugBank	APRD00435
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C5H4N4O
Molar mass	136.112 g/mol

Allopurinol is a drug used primarily to treat conditions arising from excess uric acid, most notably chronic gout. Allopurinol does not alleviate acute attacks of gout, but is useful in preventing recurrence. Allopurinol has been used in the United States since 1964.

Mechanism

Allopurinol is a structural isomer of hypoxanthine (a natually occurring purine in the body) and acts to inhibit xanthine oxidase. This enzyme is responsible for the successive oxidation of hypoxanthine and xanthine resulting in the production of uric acid, the end-product of human purine metabolism. In addition to blocking uric acid production, inhibition of xanthine oxidase causes an increase in hypoxanthine and xanthine, which are converted to closely related purine ribotides adenosine and guanosine monophosphates. Increased levels of these ribotides causes feedback inhibition of amidophosphoribosyl transferase, the first and rate-limiting enzyme of purine biosynthesis. Allopurinol therefore decreases both uric acid formation and purine synthesis.

Uses (other than in treatment of gout)

In addition to its use in gout, allopurinol is also commonly used as prophylaxis with chemotherapeutic treatments, which can rapidly result in very high uric acid concentrations due to widespread cell death (tumour lysis syndrome). Other established indications for allopurinol therapy include ischaemic reperfusion injury, kidney stones (urolithiasis) and protozoal infections (Leishmaniasis).

Metabolism

Allopurinol is rapidly metabolised by its target, xanthine oxidase, to its active metabolite oxypurinol, which is also an inhibitor of xanthine oxidase. Allopurinol is almost completely metabolised to oxypurinol within 2 hours of oral administration, whereas oxypurinol is slowly excreted by the kidney over 18-30 hours. For this reason, oxypurinol is believed responsible for the majority of allopurinol's effect.

Side effects

Side effects of allopurinol are rare, though significant when they occur. A small percentage of people develop a rash and must discontinue this drug. The most serious adverse effect is a hypersensitivity syndrome consisting of fever, skin rash, eosinophilia, hepatitis, worsening renal function and, in some cases, allopurinol hypersensitivity syndrome. Allopurinol is one of the drugs commonly known to cause Stevens-Johnson syndrome (SJS), and TENS (Toxic Epidermal Necrolysis Syndrome) which is an adverse drug reaction.

Brand names

Allopurinol is marketed by GlaxoSmithKline in the United States as Zyloprim, with other brand names including Allohexal, Progout and Zyloric.

References

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