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  • Title: Allopurinol kinetics.
    Author: Hande K, Reed E, Chabner B.
    Journal: Clin Pharmacol Ther; 1978 May; 23(5):598-605. PubMed ID: 639435.
    Abstract:
    A spectrophotometric assay for measuring allopurinol and oxipurinol has been developed which can detect as little as 5 X 10(-8) M of each in serum and urine. With this assay, serum disappearance characteristics of intravenous and orally administered allopurinol have been investigated in man. Serum concentrations of both allopurinol and oxipurinol reach levels above 1 X 10(-5) M within minutes of intravenous administration and within 1 or 2 hr of oral administration of 300 mg allopurinol. Patients receiving 300 mg allopurinol daily show a mean serum concentration of 3 X 10(-5) M oxipurinol (range, 0.9 to 9 X 10(-5) M). Serum half-lives of allopurinol and oxipurinol were 39 +/- 11 min and 13.6 +/- 2.8 hr, respectively. Estimates of renal clearance were 13.6 and 18.9 ml/min for allopurinol and 23.2 and 30.6 ml/min for oxipurinol in 2 patients studied. The metabolic conversion of allopurinol to oxipurinol in man does not appear to be altered by long-term therapy with allopurinol, which suggests that this conversion takes place by way of an enzymatic reaction not strongly inhibited by either substrate or product. These results suggest the possibility of a nonxanthine oxidase enzymatic pathway for this conversion.
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