PHARMACOKINETICS OF PIROXIMONE AFTER ORAL AND INTRAVENOUS ADMINISTRATION TO PATIENTS WITH RENAL-INSUFFICIENCY

The pharmacokinetics of piroximone (PI) were determined in patients wi th renal failure (inulin clearance less than 50 mi min-l per 1.73 m(2) ) 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 o f either 25 or 50 mg PI was given to 20 patients. PI concentrations we re assayed by h.p.l.c. in plasma and urine over 48 h. After i.v. admin istration to healthy subjects PI was distributed rapidly and eliminate d with a mean half-life of 1.3 +/- 0.2 h. The urinary recovery of unch anged PI was 64% of the dose. In the patients the extent of renal elim ination 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 C-max, AUC and t(1/2,z) values after i.v. infusion were increased by 47%, 127% and 77%, respectively, in comparison with healthy subjec ts. Similar results were obtained after oral administration. Until chr onic dosing studies are undertaken, PI dosage should be adapted in rel ation to renal function.