title: Lack of effect of hydrochlorothiazide and low-dose aspirin on the renal clearance of urate and oxypurinol after a single dose of allopurinol in normal volunteers.
abstract: OBJECTIVE
  To determine whether low-dose aspirin and hydrochlorothiazide (HCTZ) affect the renal clearance of oxypurinol and/or urate.
  
  
  METHODS
  Healthy volunteers (n = 8) were treated with allopurinol (600 mg, control), and allopurinol (600 mg) co-administered with single doses of aspirin (100 mg) or HCTZ (25 mg) or a combination of the two.
  
  
  RESULTS
  Hydrochlorothiazide, low-dose aspirin or a combination of the two, when co-administered with allopurinol, did not significantly alter (P > 0.05) the renal clearance of oxypurinol or urate. In particular, aspirin and HCTZ, when taken together and with allopurinol, did not change (P > 0.05) oxypurinol fractional renal clearance (allopurinol alone: 0.217, 0.173-0.262; combined: 0.202, 0.155-0.250) or urate fractional renal clearance (allopurinol alone: 0.066, 0.032-0.099; combined: 0.058, 0.038-0.078).
  
  
  CONCLUSIONS
  A single, low-dose of aspirin or an anti-hypertensive dose of hydrochlorothiazide, when administered alone or together with allopurinol, are unlikely to alter the hypouricaemic effect of allopurinol. The effect of chronic aspirin and HCTZ dosing taken together upon the efficacy of chronic allopurinol therapy in patients with hyperuricaemia needs to be investigated.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Xavier Level 2, Darlinghurst, NSW 2010, Australia.
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Ng
authors.forename: Sophie L
authors.initials: SL
authors.lastname: Stocker
authors.forename: Garry G
authors.initials: GG
authors.lastname: Graham
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Williams
authors.forename: Richard O
authors.initials: RO
authors.lastname: Day
mesh_terms: D000293:Adolescent; D000328:Adult; D000493:Allopurinol / Q000493:pharmacokinetics; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D001241:Aspirin / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D004232:Diuretics / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage*; D007668:Kidney / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010117:Oxypurinol / Q000493:pharmacokinetics*; D014527:Uric Acid / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004232:Diuretics; D004791:Enzyme Inhibitors; D006852:Hydrochlorothiazide; D014527:Uric Acid; D000493:Allopurinol; D010117:Oxypurinol; D001241:Aspirin