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Introduction The use of
allopurinol as a hypouricaemic acent was first explored in the 1960's and is now a
first-choice drug in the management of hyperuricaema. Allopurinol is converted almost
completely into a single active metabolite, oxypurinol, which exhibits similar inhibitory
activity of xanthine oxidase but is eliminated more slowly. Therefore, serum
concentrations of oxypurinol are greater and hence the major effects are mediated by the
rnetabolite, oxypurinol (Fig 1, see below).
A recent study has reported that in patients receiving 300 mg allopurinol daily, where
renal impairment was common, 35% of patients were receiving excessive doses of
allopurinol. Patients receiving allopurinol are at risk of developing a rare but severe
hypersensitivity syndrome, and of 600 reported cases, 26% of patients died due to a
diffuse vasculitis. The syndrome seems to be associated with the accumulation of
oxypurinol since patients with pre-existing renal disease are at greater risk.
Additionally, a major persisting problem occurs in patients who remain hyperuricaemic
despite standard doses of allopurinol. In some patients hyperuricaemia persists even when
the dose of allopurinol is increased.
It has been suggested that plasma oxypurinol concentrations of 5 - 15 mg/L, for a sample
collected 6-9 hours after the allopurinol dose, are generally effective in controlling
hyperuricaemia. Further, relying on blood urate as an index of effective control of
hyperuricaemia is complicated by diet.
Better Patient Outcomes by Individualising Allopurinol Dosage.
1. Collect a 5 mL EDTA tube for drug analysis (do not use a gel separator tube).
2. Send the sample to the laboratory using your usual transport procedures
3. Provide the following information on the request form:
"Send sample for oxypurinol to St. Vincent's Hospital, Pharmacology (8382 9184)"
and include date/time of last dose, date/time of sample collection, dose & frequency
of dosing, date/time dose regimen commenced to allow interpretation of result.
4. The patient should have received allopurinol for 5 days before a sample is collected
for evaluation, unless toxicity is suspected.
5. The sample should be collected 6-9 hours after the allopurinol dose.
Laboratory Services:
1. Oxypurinol concentration analysis will be performed weekly on Thursday.
2. Results can be obtained by phone as early as Thursday afternoon (8382 9184).
Further Information
St. Vincent's Hospital - NSW Referral Laboratory for Therapeutic Drug Monitoring Further
information John Ray (02) 8382 9190.
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