Use and abuse of allopurinol.

Out of hours investigations are no longer used exclusively for diagnosis leading to urgent treatment. Deleting tests that do not meet traditional criteria of urgency might thus lead to additional costs for example, by delaying discharge of a patient at the weekend or necessitating earlier admission so that preoperative tests could be done during normal working hours. Although the need to reduce costs is obvious, the reductions must be both financially worthwhile and not affect patient care. Reducing laboratory work done out of hours probably does not meet these criteria. The cost and effectiveness of laboratory investigations need to be improved by day as well as by night, using a strategy that will influence the requesting practices of doctors." Reducing laboratory costs should not be the primary motivation for doing this. 5 Winkelman JW. Less utilisation of the clinical laboratory produces disproportionally small true cost reductions. 9 Lester E. A new strategy for out-of-hours laboratory investigations. Allopurinol was first synthesised as an adjunct to anticancer treatment with mercaptopurine in 1960 but was found to have powerful hypouricaemic effects.' It has caused severe tophaceous gout to all but vanish, and renal complications of gout are now rare.2 Recently a controlled trial has confirmed that allopurinol can inhibit the formation of calcium oxalate stones in the 15-20% ofpatients who form stones and who are hyperuricosuric.3 More than 5 million patient years of treatment have now accumulated, and more than 70 tonnes of what is in general a safe and effective agent are ingested each year. Minor reactions to the drug do occur-probably 2% of patients will develop itching and rashes.4 More severe reactions, including exfoliative dermatitis or toxic epider-molysis, eosinophilia with interstitial nephritis or vasculitis, hepatic granulomas, and bone marrow depression have been described in about 350 patients,5-23 with a further 250 unpublished cases (G Lovett, personal communication). Many ofthose suffering severe reactions had reduced renal function and often the dose of allopurinol used was either not stated or was too high for the degree of renal function.7~22 We believe that these toxic effects could mostly have been avoided by better understanding of the metabolism and renal handling of the drug. About 60-70% of allolpurinol is metabolised to its active principle, oxipurinol, which is excreted through the kidney together with allopurinol itself and allopurinol riboside, the second main metabolite.2' Unlike allopurinol and its ribo-side, which are rapidly cleared, oxipurinol undergoes net reabsorption …