Renal changes associated with naproxen sodium administration in cynomolgusmonkeys

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 mmonke ys/gender) or of 44 mg/kg for 13 wk (4 monkeys/gender). Body weight loss oc curred 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 in creases in creatinine and/or serum urea nitrogen values as well as higher r enal weights occurred in monkeys receiving 176 mg/kg for 2 wk or 44 mg/kg f or 13 wk. Microscopically, renal changes were observed in all naproxen sodi um-dosed groups. Renal Endings after 2 wk of exposure included increased in terstitial ground substance, tubular dilatation, and tubulointerstitial nep hritis; in the 13-wk study, conical tubular atrophy and interstitial fibros is were also observed. These studies identify the kidney as the target orga n of naproxen sodium in cynomolgus monkeys.