Allopurinol sensitivity: Report of two cases

An high-pressure liquid chromatographic method was used to measure allopurinol and oxipurinol in plasma and urine in 6 healthy volunteers after a single intravenous or oral dose of allopurinol. The influence of coadministered benzbromarone and hydrochlorothiazide on the pharmacokinetics of allopurinol and oxipurinol was also investigated. After intravenous injection of allopurinol 300 mg the plasma disappearance was biexponential, with a mean distribution half-life of 2.32 +/- 1.08 min (mean +/- SD) and an elimination half-life of 47.8 +/- 10.6 min. The total clearance of allopurinol was 11.37 +/- 2.70 ml/min/kg, whereas its renal clearance was only 1.73 +/- 0.79 ml/min/kg. Oxipurinol disappeared monoexponentially from plasma with a mean half-life of 12.2 +/- 2.6 h. Its renal clearance was 0.42 +/- 0.091 ml/min/kg. After oral administration of allopurinol 300 mg the peak plasma concentration of 2.1 +/- 0.6 micrograms/ml (1.5 x 10(-5) M) was reached within 30 to 120 min. The peak level of oxipurinol of 5.8 +/- 1.5 micrograms/ml (3.8 x 10(-5) M) was found within 2 to 5 h after intravenous and oral allopurinol. The bioavailability of oral allopurinol computed from plasma data was 90.4 +/- 8.7%. The total recovery from urine was 77% (allopurinol 8%, oxipurinol 69%) after oral and 88% after i.v. administration. It was concluded that about 10% of the oral dose was not absorbed and that 12% was eliminated by an unknown mechanism, presumably as riboside. The pharmacokinetics of allopurinol and oxipurinol were not significantly influenced by coadministration of benzbromarone or hydrochlorothiazide.

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Allopurinol Hypersensitivity: A Systematic Review of All Published Cases, 1950–2012

Ramasamy

et al. 2013

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Risk factors associated with AH, such as concomitant diuretic use, pre-existing renal impairment and recent initiation of allopurinol, were commonly present in AH patients; however, their role in the mechanism of AH remains to be established. A clear risk factor was the HLA-B*5801 status; this was especially relevant in Asian populations where there is a higher carriage rate of the allele. High allopurinol dose, previously suggested to be a risk factor, was not confirmed as such. The paucity of well-documented case reports and studies of AH render it difficult to draw more concrete conclusions or construct a meticulous profile of patients at risk of AH. Future case reports of AH need to be better documented to contribute to understanding the risks for, and mechanisms of, AH.

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Allopurinol sensitivity: Report of two cases

Cited by 4 publications

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The Development of Allopurinol

The Development of Allopurinol

Kinetics of allopurinol after single intravenous and oral doses

Allopurinol Hypersensitivity: A Systematic Review of All Published Cases, 1950–2012

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