title: Impaired response or insufficient dosage? Examining the potential causes of "inadequate response" to allopurinol in the treatment of gout.
abstract: OBJECTIVE
  Gout is one of the most common forms of arthritis. It is well established that urate-lowering therapy that aims for a serum urate less than at least 0.36 mmol/l (6 mg/dl) is required for the successful management of gout. Allopurinol, a xanthine oxidase (XO) inhibitor, is the most commonly used urate-lowering therapy. However, many patients fail to achieve the target serum urate on allopurinol; these patients can be considered to have "inadequate response" to allopurinol. Herein, we examine the potential mechanisms and implications of inadequate response to allopurinol.
  
  
  METHODS
  The literature was reviewed for potential causes for failure to reach target serum urate in patients receiving allopurinol.
  
  
  RESULTS
  The two most common causes of inadequate response to allopurinol are poor adherence and under-dosing of allopurinol. Adherent patients who fail to achieve target serum urate on standard doses of allopurinol form a group that could be considered to be "partially resistant" to allopurinol. There are four potential mechanisms for partial allopurinol resistance: decreased conversion of allopurinol to oxypurinol; increased renal excretion of oxypurinol; abnormality in XO structure and/or function such that oxypurinol is rendered less effective and/or drug interactions.
  
  
  CONCLUSIONS
  It is important to determine the reasons for failure to achieve treatment targets with allopurinol, particularly as newer agents become available. The knowledge of the mechanisms for inadequate response may help guide the clinician towards making a therapeutic choice that is more likely to result in achieving the serum urate target.
authors.affiliation: Department of Medicine, University of Otago, Christchurch, P.O. Box 4345, Christchurch 8140, New Zealand. Electronic address: lisa.stamp@cdhb.health.nz.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Stamp
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Tony R
authors.initials: TR
authors.lastname: Merriman
authors.affiliation: Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand.
authors.forename: Murray L
authors.initials: ML
authors.lastname: Barclay
authors.affiliation: Medicine Service, Birmingham VA Medical Center, Birmingham, AL; Rheumatology Division, University of Alabama, Birmingham, AL.
authors.forename: Jasvinder A
authors.initials: JA
authors.lastname: Singh
authors.affiliation: Department of Surgical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Roberts
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors.forename: Daniel F B
authors.initials: DF
authors.lastname: Wright
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: Nicola
authors.initials: N
authors.lastname: Dalbeth
mesh_terms: D000493:Allopurinol / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006073:Gout / Q000097:blood / Q000188:drug therapy*; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D010349:Patient Compliance; D017211:Treatment Failure; D014527:Uric Acid / Q000097:blood
chemical_list: D015415:Biomarkers; D006074:Gout Suppressants; D014527:Uric Acid; D000493:Allopurinol
keywords: Allopurinol; Drug resistance; Gout; Oxypurinol