What is the half-life of allopurinol in an adult patient with a history of gout and possible impaired renal function?

Half-Life of Allopurinol

Allopurinol has a plasma half-life of approximately 1-2 hours, while its active metabolite oxypurinol has a significantly longer half-life of approximately 15-23 hours in patients with normal renal function. 1

Pharmacokinetic Profile

Allopurinol (Parent Drug)

• The elimination half-life of allopurinol is 1.2 ± 0.3 hours (mean ± SD) in patients with normal renal function 2
• Allopurinol is rapidly absorbed and extensively metabolized to its active metabolite oxypurinol, with approximately 90% conversion 2
• Peak plasma levels occur at approximately 1.5 hours after oral administration 1
• Because of its rapid oxidation to oxypurinol and renal clearance rate approximately equal to glomerular filtration rate, allopurinol is cleared quickly from the body 1

Oxypurinol (Active Metabolite)

• Oxypurinol has a much longer plasma half-life of approximately 15-23 hours in patients with normal renal function, which is the primary reason for effective xanthine oxidase inhibition over a 24-hour period with once-daily dosing 1, 2
• Peak plasma levels of oxypurinol occur at approximately 4.5 hours after allopurinol administration 1
• The pharmacokinetic parameters of oxypurinol in subjects with normal renal function include a half-life of 23.3 ± 6.0 hours 2

Impact of Renal Impairment

In patients with severely impaired renal function or decreased urate clearance, the half-life of oxypurinol in the plasma is greatly prolonged. 1

• Oxypurinol is cleared almost entirely by urinary excretion (>95%), making renal function the primary determinant of its elimination 2, 3
• The elimination half-life of oxypurinol is 18-30 hours in those with normal kidney function but becomes significantly prolonged in renal impairment 3
• In patients with moderate to severe renal impairment, oxypurinol clearance is dramatically reduced: apparent clearance decreases from 1.8 L/h in normal renal function to 0.6 L/h in mild impairment, 0.3 L/h in moderate impairment, and 0.18 L/h in severe impairment 4
• A dose reduction of 50% is recommended in patients with renal insufficiency due to prolonged oxypurinol half-life 5, 1

Clinical Implications

• The long half-life of oxypurinol allows for once-daily dosing of allopurinol and maintains therapeutic xanthine oxidase inhibition throughout the day 1
• Uric acid may return to pretreatment levels slowly (usually after 7-10 days) following cessation of therapy, reflecting primarily the accumulation and slow clearance of oxypurinol 1
• In patients with severely impaired renal function, a dose of 100 mg per day or 300 mg twice a week may be sufficient to maintain adequate xanthine oxidase inhibition due to the greatly prolonged oxypurinol half-life 1