Half-Life of Allopurinol
Allopurinol has a plasma half-life of approximately 1-2 hours, while its active metabolite oxipurinol has a much longer half-life of approximately 15 hours. 1
Pharmacokinetic Profile of Allopurinol
Allopurinol is rapidly and extensively absorbed from the gastrointestinal tract with approximately 90% absorption 1. After oral administration, allopurinol demonstrates the following pharmacokinetic parameters:
- Bioavailability: 79 ± 20% 2
- Peak plasma levels: Occur at approximately 1.5 hours after ingestion 1
- Half-life of allopurinol: 1-2 hours 1, 2
- Half-life of oxipurinol: Approximately 15 hours 1, 2
- Clearance: Primarily by glomerular filtration 1
Metabolism and Active Metabolite
Allopurinol is rapidly metabolized to its active metabolite oxipurinol (also called alloxanthine), which is responsible for much of the drug's therapeutic effect:
- Allopurinol is quickly converted to oxipurinol through oxidation 1
- Oxipurinol is also an inhibitor of xanthine oxidase 1
- Peak plasma levels of oxipurinol occur at approximately 4.5 hours after allopurinol administration 1
- After a single 300 mg oral dose, maximum plasma levels reach approximately 3 mcg/mL for allopurinol and 6.5 mcg/mL for oxipurinol 1
Elimination
The elimination pathways for allopurinol and oxipurinol differ significantly:
- Allopurinol: Cleared primarily by glomerular filtration and rapid conversion to oxipurinol 1
- Oxipurinol: Reabsorbed in the kidney tubules in a manner similar to uric acid reabsorption 1
- Approximately 20% of ingested allopurinol is excreted in the feces 1
- Up to 80% of allopurinol is recovered in the urine within 24 hours, mainly in the form of oxipurinol 3
Clinical Implications
The short half-life of allopurinol but long half-life of its active metabolite oxipurinol has important clinical implications:
- Effective xanthine oxidase inhibition is maintained over a 24-hour period with single daily dosing due to oxipurinol's longer half-life 1
- In patients with renal impairment, oxipurinol can accumulate, requiring dose adjustment 1, 3
- The renal clearance of oxipurinol is directly proportional to creatinine clearance 4
- When allopurinol is used with uricosuric agents, the clearance of oxipurinol increases, which can affect dosing requirements 1
Special Considerations
- Drug interactions: Allopurinol inhibits the metabolism of 6-mercaptopurine and azathioprine, requiring dose reductions of these medications by 65-75% when used concomitantly 5
- Renal impairment: Dose reduction is recommended in patients with renal insufficiency to prevent toxicity 4
- Peritoneal dialysis: In patients on peritoneal dialysis, oxypurinol and urate are removed by the dialysis process, accounting for more than 50% of their clearance 6
Understanding the half-life of allopurinol and its active metabolite oxipurinol is crucial for appropriate dosing and monitoring, particularly in patients with renal impairment or those taking interacting medications.