Allopurinol dosage selection: relationships between dose and plasma oxipurinol and urate concentrations and urinary urate excretion.

Abstract

1 Allopurinol usage in 50 patients of a city teaching hospital was surveyed. 2 The plasma concentrations of oxipurinol and uric acid and the urinary production of uric acid were examined. 3 The daily doses of allopurinol ranged from 50 to 1200 mg but 83% of patients were taking 300 mg daily. 4 A wide range of plasma oxipurinol concentrations was observed from 2.8 to 55.8mg 11 with a mean ± s.d. of 15.2 ± 11.7 mg l-1. 5 The population studied included a high proportion of patients with renal impairment and creatinine clearance was a significant determinant of oxipurinol concentrations (P < 0.005). 6 There was no significant correlation between plasma urate and plasma oxipurinol concentrations and only a few plasma urates were above the upper limit of the reference range of the laboratory. 7 It was apparent that many patients were taking unnecessarily high daily doses of allopurinol and that renal status was not always considered when deciding dosage regimens of allopurinol.

Pharmacodynamics of oxypurinol after administration of allopurinol to healthy subjects

“…The renal clearance of urate may have been a contributing appropriate for these data. This result is in contrast to the estimated value of c for the 1MU/1MX response factor in the patient study [ 15] as many patients in the study group had decreased renal function. Also, starting data (8.92±3.91) which is large in comparison.…”

“…The C 90 in this study (5.13 mg l−1) confirms the further suggests that patients are being treated with excessively high doses of allopurinol as it was found finding that the mean oxypurinol concentrations found during routine therapy with standard doses of allothat the mean oxypurinol concentration of patients treated with standard doses of allopurinol (usually purinol (15.2 mg l−1; 100 m) [ 15], is far in excess of that required to inhibit the activity of xanthine oxidase, 300 mg day−1) is 15.2 mg l−1 while 32% of the patient population had oxypurinol concentrations higher than suggesting that patients in general are given excessive doses of allopurinol.…”

“…As a (Figure 3 ). In a previous cross-sectional study conducted in patients receiving allopurinol therapy there was no result, the standard dose of allopurinol of 300 mg day−1 may be a reasonable therapeutic dose for treatment in significant correlation between plasma urate and plasma oxypurinol concentrations [15 ]. Plasma urate concenmany individuals.…”

“…15 mg l−1 [15 ]. However, the current study was carried out in healthy volunteers with normal plasma concenThe effect of increasing plasma oxypurinol concentration on the concentration of plasma urate was trations of urate in vivo and normal renal function.…”

Relationship between plasma oxipurinol concentrations and xanthine oxidase activity in volunteers dosed with allopurinol.

“…However, the concentration term in this expression had to be raised to various powers (n ranged from 2 to 6.4) to achieve a satisfactory fit of the data, an approach pioneered by Hill (1910) and related to the 'Sigmoid E max Model' (Holford & Sheiner, 1981). The EC50 and go derived using this approach were remarkably low (1.4 and 4.08 mg 11 respectively) given that the average plasma oxipurinol concentrations found in populations of hospital patients given allopurinol is around 15 mg 1-1 (Emmerson et al, 1987;Day et al, 1988). This might suggest that, in general, patients are being given excessive doses of allopurinol.…”