title: Relationship between serum urate and plasma oxypurinol in the management of gout: determination of minimum plasma oxypurinol concentration to achieve a target serum urate level.
abstract: The treatment of gout requires a lowering of serum urate (SU) levels, and allopurinol is the drug that is most commonly used for this purpose. The objectives of this study were to define the relationships between allopurinol dose on the one hand and plasma oxypurinol, renal function, and SU levels on the other and to determine the minimum plasma oxypurinol concentration that would result in a target level of <6 mg/dl (0.36 mmol/l) of SU. For this purpose, 82 patients who had been receiving allopurinol for at least 1 month were recruited. Patients with SU <6 mg/dl were followed up quarterly for 12 months. In patients with SU ≥6 mg/dl, the dose of allopurinol was increased to bring the level of SU to <6 mg/dl. These patients were followed up once a month until the SU level remained at <6 mg/dl for 3 consecutive months; thereafter they were seen quarterly. SU, creatinine, and plasma oxypurinol were measured 6-9 hours after administration of the allopurinol dose. There were significant inverse correlations between creatinine clearance (CrCl) and plasma oxypurinol (P = 0.002), between allopurinol dose and SU (P < 0.0001) and between plasma oxypurinol and SU (P < 0.0001). Using receiver operating characteristic analysis, the target SU of <6 mg/dl was achieved in 75% of serum samples with plasma oxypurinol levels of >100 µmol/l (15.2 mg/l). Increasing the allopurinol dose resulted in increased plasma oxypurinol and reduced SU concentrations. Plasma oxypurinol concentrations >100 µmol/l were required to achieve SU <6 mg/dl.
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand. lisa.stamp@cdhb.govt.nz
authors.forename: L K
authors.initials: LK
authors.lastname: Stamp
authors.forename: M L
authors.initials: ML
authors.lastname: Barclay
authors.forename: J L
authors.initials: JL
authors.lastname: O'Donnell
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Drake
authors.forename: C
authors.initials: C
authors.lastname: Frampton
authors.forename: P T
authors.initials: PT
authors.lastname: Chapman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D015210:Arthritis, Gouty / Q000188:drug therapy*; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000097:blood* / Q000378:metabolism; D005260:Female; D006073:Gout / Q000097:blood / Q000188:drug therapy*; D006074:Gout Suppressants / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010117:Oxypurinol / Q000009:adverse effects / Q000097:blood* / Q000378:metabolism; D059039:Standard of Care; D014527:Uric Acid / Q000097:blood*
chemical_list: D004791:Enzyme Inhibitors; D006074:Gout Suppressants; D014527:Uric Acid; D000493:Allopurinol; D003404:Creatinine; D010117:Oxypurinol