Pharmacokinetic study of the new sulfamethopyrazine-trimethoprim combination (kelfiprim) in renal insufficiency.
The combination of trimethoprim (TMP) and sulfamethopyrazine (SMP) has been successfully used to treat chronic urinary tract infections. Since parenchymal involvement associated with renal insufficiency of varying degree is not infrequent in these patients, it was considered important to study the pharmacokinetics of TMP and SMP in a fixed dose combination. Four groups of patients were studied: 1) 4 patients with endogenous creatinine clearance (CLcR) between 80 and 40 ml/min; 2) 3 patients with CLcR between 40 and 10 ml/min; 3) 3 patients on chronic peritoneal dialysis (CAPD); and 4) 3 patients on haemodialysis. A single oral dose of 250 mg TMP and 200 mg SMP was given to each patient. Multiple samples were collected over 9 days and the following pharmacokinetic parameters were calculated: total area under the plasma level curve, slow disposition rate constant beta and the corresponding t1/2 beta, plasma clearance and the apparent volume of distribution. The results show that the two moieties of the TMP-SMP combination behaved differently in uraemic patients as fas as elimination rate was concerned. TMP was eliminated more slowly both in patients with diminished renal function and in those subjected to haemo- or peritoneal dialysis. The reduction in the rate of elimination of TMP was significantly correlated with the degree of renal impairment. The elimination of SMP, however, was not significantly affected by the reduced renal function; indeed a tendency to increase was noted, at least in dialyzed patients.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000368:Aged; D004338:Drug Combinations / Q000378:metabolism; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013415:Sulfalene / Q000378:metabolism*; D013424:Sulfanilamides / Q000378:metabolism*; D014295:Trimethoprim / Q000378:metabolism*
D004338:Drug Combinations; D013424:Sulfanilamides; C026911:kelfiprim; D014295:Trimethoprim; D013415:Sulfalene