title: Renal changes associated with naproxen sodium administration in cynomolgus monkeys.
abstract: Naproxen sodium was administered to cynomolgus monkeys (Macaca fascicularis) by oral gavage at daily doses of 44, 88, or 176 mg/kg for 2 wk (2 monkeys/gender) or of 44 mg/kg for 13 wk (4 monkeys/gender). Body weight loss occurred in at least one monkey in all naproxen sodium-dosed groups in the 2-wk (up to 16% loss) and 13-wk (up to 22% loss) studies. Increases in plasma naproxen concentrations were dose proportional between 44 and 88 mg/kg but were less than dose proportional between 88 and 176 mg/kg. Up to 2-fold increases in creatinine and/or serum urea nitrogen values as well as higher renal weights occurred in monkeys receiving 176 mg/kg for 2 wk or 44 mg/kg for 13 wk. Microscopically, renal changes were observed in all naproxen sodium-dosed groups. Renal findings after 2 wk of exposure included increased interstitial ground substance, tubular dilatation, and tubulointerstitial nephritis; in the 13-wk study, cortical tubular atrophy and interstitial fibrosis were also observed. These studies identify the kidney as the target organ of naproxen sodium in cynomolgus monkeys.
authors.affiliation: Schering-Plough Research Institute, Lafayette, New Jersey 07848, USA. michael.leach@spcorp.com
authors.forename: M W
authors.initials: MW
authors.lastname: Leach
authors.forename: D W
authors.initials: DW
authors.lastname: Frank
authors.forename: M R
authors.initials: MR
authors.lastname: Berardi
authors.forename: E W
authors.initials: EW
authors.lastname: Evans
authors.forename: R C
authors.initials: RC
authors.lastname: Johnson
authors.forename: D G
authors.initials: DG
authors.lastname: Schuessler
authors.forename: E
authors.initials: E
authors.lastname: Radwanski
authors.forename: M E
authors.initials: ME
authors.lastname: Cartwright
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D003238:Connective Tissue / Q000187:drug effects / Q000473:pathology; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology; D008252:Macaca fascicularis; D008297:Male; D009288:Naproxen / Q000493:pharmacokinetics / Q000633:toxicity*; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010865:Pilot Projects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen; D003404:Creatinine