Table 2.

Pharmacokinetics of oxypurinol and the pharmacodynamic effects of allopurinol alone or with probenecid for at least 7 days (500 or 1000 mg/day) in patients with gout. Data are mean (95% CI).

VariableAllopurinol, n = 19Allopurinol and Probenecid (500 mg/day), n = 19Allopurinol and Probenecid (1000 mg/day), n = 7
Plasma urate concentrations and renal and fractional renal clearances
  CUA, mmol/l0.37 (0.34–0.41)0.28 (0.24–0.31)*
  CLR(UA), ml/min6.0 (4.4–7.5)9.6 (6.9–12.3)**
  CLR(CR), ml/min125.0 (105.1–144.8)109.1 (88.4–129.8)***
  CLR(UA/CR) ratio0.046 (0.038–0.054)0.088 (0.072–0.104)*
Plasma oxypurinol concentrations and total, renal, and fractional renal clearances
  Cav,ss, mg/l11.1 (5.0–17.3)8.2 (4.0–12.4)*
  CL/F, ml/min16.2 (10.3–22.1)21.9 (14.6–29.2)*
  CLR(OXY), ml/min12.7 (9.8–15.6)16.1 (12.3–19.9)***
  CLR(OXY/CR) ratio0.098 (0.083–0.114)0.140 (0.117–0.163)*
Patients who received both 500 mg and 1000 m daily probenecid
Plasma urate concentrations and renal and fractional renal clearances
  CUA, mmol/l0.43 (0.35–0.50)0.34 (0.27–0.41)**0.27 (0.21–0.34)**††
  CLR(UA), ml/min4.8 (1.8–7.8)8.9 (4.0–13.8)**10.4 (5.4–15.5)**
  CLR(CR), ml/min120 (70–171)107 (59–155)110 (66–155)
  CLR(UA/CR) ratio0.038 (0.027–0.050)0.089 (0.047–0.110)**0.094 (0.053–0.136)**
Plasma oxypurinol concentrations and total, renal, and fractional renal clearances
  Cav,ss, mg/l12.4 (3.2–21.6)8.9 (2.9–14.9)***8.7 (2.4–14.7)***
  CL/F, ml/min14.7 (7.4–22.0)19.7 (11.3–28.2)**21.3 (12.1–30.4)**
  CLR(OXY), ml/min10.0 (3.1–16.9)12.9 (6.2–19.6)16.5 (8.3–24.6)***#
  CLR(OXY/CR) ratio0.082 (0.045–0.118)0.116 (0.068–0.163)***0.146 (0.098–0.194)**
  • Subscripts: oxypurinol (OXY), urate (UA), and creatinine (CR). Cav,ss: average steady-state plasma concentration derived from NONMEM (daily doses of allopurinol ranged from 100 to 300 mg/day); CLR: renal clearance; CLR(OXY/CR): fractional renal clearance of oxypurinol; CLR(UA/CR): fractional renal clearance of urate; CL/F: apparent total body clearance of oxypurinol derived from NONMEM.

  • * p < 0.001;

  • ** p < 0.01;

  • *** p < 0.05 versus allopurinol monotherapy;

  • one subject achieved plasma urate < 0.3 mmol/l with the addition of probenecid 250 mg/day.

  • †† p < 0.01;

  • # p < 0.05 versus allopurinol and probenecid 500 mg daily.