Stereoselective disposition of ibuprofen in patients with renal dysfunction

Ibuprofen-induced acute renal failure is thought to occur in clinical conditions where maintenance of renal function is prostaglandin-dependent. In this study we used a pharmacokinetic approach to assess the predisposing factors for this therapeutic pitfall. The pharmacokinetics of ibuprofen enantiomers was examined after a single dose of 800 mg of racemic ibuprofen in three groups of subjects: A) patients with pre-existing renal failure (n = 10); B) patients with underlying disease states other than renal failure (n = 11); and C) age-matched healthy controls (n = 10). Most of the patients with renal insufficiency showed elevated plasma (S)-ibuprofen levels, higher area under plasma concentration vs. time curve for (S)-ibuprofen and increased area under plasma concentration vs. time curves for (S)-/(R)-ibuprofen ratios as compared with their healthy counterparts. It appeared that the extent of metabolic activation of (R)-ibuprofen to the (S)-isomer in renally compromised patients was greater than that in a normal setting. Consequently, in susceptible patients, reduced renal clearance coupled with concomitant metabolic inversion leads to elevated (S)-ibuprofen levels which may exacerbate the ischemic effect as a result of the accentuated blockage of prostaglandin synthesis.