Assessment of ibuprofen-associated nephrotoxicity in renal dysfunction.

Ibuprofen-incurred nephrotoxicity in renal insufficiency was assessed by examining renal functional and pathological changes in rabbits with pre-existing renal failure after receiving consecutive doses of ibuprofen. The pharmacokinetic behavior of ibuprofen enantiomers in rabbits with renal dysfunction appeared to qualitatively parallel that of their human counterparts. Modifications of the pharmacokinetic profile occurred in a stereoselective fashion: (R)-ibuprofen disposition was independent of renal conditions, whereas (S)-ibuprofen clearance was significantly hampered. Pathological damage associated with ibuprofen use in renal dysfunction was evident from the renal necropsy specimens, which was characterized by tubular necrosis and interstitial nephritis. This animal model study indicates clearly that renal insufficiency is a causative factor for ibuprofen-induced interstitial nephritis. Moreover, based on the evidence of interstitial lymphocytic infiltration, this nephrotoxic syndrome is assumed to be a manifestation of a disordered cellular immunity.