Pharmacokinetics of piroximone after oral and intravenous administration to patients with renal insufficiency.

The pharmacokinetics of piroximone (PI) were determined in patients with renal failure (inulin clearance less than 50 ml min-1 per 1.73 m2) using two protocols: (a) 10 patients received a single i.v. infusion of 0.5 mg kg-1 PI and the data were compared with those from seven healthy subjects receiving the same regimen; (b), a single oral dose of either 25 or 50 mg PI was given to 20 patients. PI concentrations were assayed by h.p.l.c. in plasma and urine over 48 h. After i.v. administration to healthy subjects PI was distributed rapidly and eliminated with a mean half-life of 1.3 +/- 0.2 h. The urinary recovery of unchanged PI was 64% of the dose. In the patients the extent of renal elimination of PI was decreased (-78%) in relation to the degree of renal insufficiency as assessed by inulin clearance (r = 0.97, P < 0.0001). Mean Cmax, AUC and t1/2,z values after i.v. infusion were increased by 47%, 127% and 77%, respectively, in comparison with healthy subjects. Similar results were obtained after oral administration. Until chronic dosing studies are undertaken, PI dosage should be adapted in relation to renal function.