Effect of chronic renal failure on oxaprozin multiple-dose pharmacokinetics.
The effects of renal disease on the steady-state kinetics of oxaprozin were assessed in eight patients on hemodialysis with normal serum albumin levels and eight normal subjects who received six doses. A larger clearance and volume of distribution at steady state for total and unbound oxaprozin occurred in the patients on hemodialysis. The elimination half-lives were not different. The mean total AUC, peak concentration, average steady-state plasma concentration, and trough concentration for total and unbound oxaprozin were decreased in the patients on hemodialysis. These differences are consistent with impaired absorption of oxaprozin in patients on hemodialysis. The higher dose-averaged unbound fraction of oxaprozin in plasma in patients on hemodialysis may be caused by endogenous binding inhibitors. Because clearance was not reduced in patients on hemodialysis, the dose of oxaprozin may not need to be reduced when albumin levels are normal.
Audet
P R
PR
Renal Electrolyte Section, Hospital of the University of Pennsylvania, Philadelphia.
Knowles
J A
JA
Troy
S M
SM
Walker
B R
BR
Morrison
G
G
D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D000077431:Oxaprozin; D011422:Propionates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011485:Protein Binding; D006435:Renal Dialysis; D012709:Serum Albumin / Q000032:analysis / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011422:Propionates; D012709:Serum Albumin; D000077431:Oxaprozin