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Oxaprozin disposition in renal disease
Author(s) -
Chiang Soong T,
Morrison Gail,
Knowles John A,
Ruelius Hans W,
Walker Barry R
Publication year - 1982
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1982.68
Subject(s) - volume of distribution , azotemia , chemistry , hemodialysis , pharmacology , pharmacokinetics , distribution (mathematics) , rheumatoid arthritis , medicine , renal function , mathematical analysis , mathematics
Effects of renal disease on the disposition kinetics of oxaprozin, a nonsteroidal antiinflammatory analgesic, were assessed in 15 subjects who were normal, renally impaired, or who had been undergoing hemodialysis. Oral dose clearance (Cl oral ), volume of distribution at steady‐state (V ss d ), and elimination half‐life (t l / 2 ) did not substantially differ among the three groups. Mean fraction unbound oxaprozin in plasma (f up ) increased from 0.08% in the normal group to 0.18% and 0.28% in the two azotemic groups. Consequently, unbound drug kinetic parameters, including intrinsic clearance (Cl int ) and V ss du of unbound drug were reduced from 2.9 l/hr/kg and 193 l/kg in normal subjects to approximately 1.6 l/hr/kg and 91 l/kg in azotemic patients. The smaller volume of distribution is consistent with a decrease in oxaprozin tissue binding in azotemia. The decreased plasma and tissue binding and lower Cl int suggest that, in the treatment of azotemic patients with rheumatoid arthritis, the dose of oxaprozin should begin at 600 mg once a day. Clinical Pharmacology and Therapeutics (1982) 31, 509–515; doi: 10.1038/clpt.1982.68