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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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.[1]

References

  1. Stereoselective disposition of ibuprofen in patients with renal dysfunction. Chen, C.Y., Chen, C.S. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
 
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