Pharmacokinetic comparison of flurbiprofen in end-stage renal disease subjects and subjects with normal renal function.
This study compared the pharmacokinetics of flurbiprofen (F) and three major metabolites in patients with end-stage renal disease (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD) with the pharmacokinetics of F in normal subjects. A single 100-mg dose of F was administered to each of nine normal subjects and eight ESRD subjects. Blood and urine samples were collected in both groups; serial and end of dwell dialysate samples were obtained from the ESRD subjects. Plasma was analyzed for both the R and S optical isomers of F and its major metabolite, 4'-hydroxy-flurbiprofen (HF). Urine and dialysate were analyzed for F and three known metabolites. Plasma concentrations of F in the ESRD subjects were approximately 50% of the values obtained from the normal subjects (P less than .05). Flurbiprofen half-life and Tmax were not different. Elimination of HF was reduced in ESRD subjects. Urinary data suggest that HF was the major metabolite excreted (36% of the dose) in normal subjects whereas 3',4'-dihydroxy-flurbiprofen was the major metabolite (9% of the dose) excreted in the ESRD group. Mean urinary recovery of the dose was 73% in the normal subjects, but only 16% in ESRD subjects. Neither F nor its metabolites were detected in dialysate. Small enantiomer differences were seen. This study suggests that ESRD subjects have lower plasma levels of F than normal subjects when administered equal size doses. Accumulation of metabolites may occur in ESRD subjects upon multiple dosing. Enantiomer differences are not clinically significant.
Cefali
E A
EA
Department of Pharmacy and Pharmaceutics, Virginia Commonwealth University-Medical College of Virginia, Richmond.
Poynor
W J
WJ
Sica
D
D
Cox
S
S
D000328:Adult; D005260:Female; D005480:Flurbiprofen / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D015312:Hemodialysis Solutions / Q000032:analysis; D006801:Humans; D007536:Isomerism; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory
D015312:Hemodialysis Solutions; C065522:4'-hydroxyflurbiprofen; D005480:Flurbiprofen; C073814:3',4'-dihydroxyflurbiprofen; C073815:3'-hydroxy-4'-methoxyflurbiprofen