title: Predicting allopurinol response in patients with gout.
abstract: OBJECTIVE
  The primary aim of this research was to predict the allopurinol maintenance doses required to achieve the target plasma urate of ≤0.36 mmol l(-1) .
  
  
  METHODS
  A population analysis was conducted in nonmem using oxypurinol and urate plasma concentrations from 133 gout patients. Maintenance dose predictions to achieve the recommended plasma urate target were generated.
  
  
  RESULTS
  The urate response was best described by a direct effects model. Renal function, diuretic use and body size were found to be significant covariates. Dose requirements increased approximately 2-fold over a 3-fold range of total body weight and were 1.25-2 fold higher in those taking diuretics. Renal function had only a modest impact on dose requirements.
  
  
  CONCLUSIONS
  Contrary to current guidelines, the model predicted that allopurinol dose requirements were determined primarily by differences in body size and diuretic use. A revised guide to the likely allopurinol doses to achieve the target plasma urate concentration is proposed.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin.
authors.forename: Daniel F B
authors.initials: DF
authors.lastname: Wright
authors.affiliation: School of Pharmacy, University of Otago, Dunedin.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Duffull
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin.
authors.forename: Tony R
authors.initials: TR
authors.lastname: Merriman
authors.affiliation: Department of Medicine, University of Auckland, Auckland.
authors.forename: Nicola
authors.initials: N
authors.lastname: Dalbeth
authors.affiliation: Department of Medicine, University of Otago, Christchurch.|Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand.
authors.forename: Murray L
authors.initials: ML
authors.lastname: Barclay
authors.affiliation: Department of Medicine, University of Otago, Christchurch.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Stamp
mesh_terms: D000493:Allopurinol / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D006073:Gout / Q000097:blood / Q000188:drug therapy*; D006074:Gout Suppressants / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010117:Oxypurinol / Q000097:blood*; D011237:Predictive Value of Tests; D014527:Uric Acid / Q000097:blood*
chemical_list: D006074:Gout Suppressants; D014527:Uric Acid; D000493:Allopurinol; D010117:Oxypurinol
keywords: allopurinol; gout; nonmem; pharmacokinetic-pharmacodynamics