Biotransformation sulindac

The major urinary metabolites are sulindac and its glucuronide, sulfone and its glucuronide and in trace amounts the insoluble sulfide metabolite and its glucuronide. The major biotransformation involves irreversible oxidation of the sulfoxide group of sulindac to sulfone and a reversible reduction to the sulfide. Studies in healthy subjects revealed that after oral administration of sulindac at least 88% is absorbed. After a single 200 mg oral dose the peak plasma concentrations of sulindac and its sulfone and sulfide metabolites were 4, 2, and 3 mg/ml respectively, and were attained after 1 hour for the parent drug and after 2 hours for each of the metabolites. 

A typical example of an effective bioprecursor prodrug is given by the anti-inflammatory drug sulindac. Sulindac, di-5-fluoro-2-methyl-l-[p-(methylsulfinyl) benzylidene] indene-3 acetic acid is a non-steroidal anti-inflammatory agent having a broad spectrum of activity in animal models and in man. The two quantitatively significant biotransformations undergone by sulindac in laboratory species and... 

Figure 10 Oxidative and reductive human biotransformations of sulindac in vivo. Racemic sulindac sulfoxide, a prodrug, is reversibly reduced to the active sulfide metabolite, which is reoxidized to either the R- or the S-sulfoxide enantiomer. The sulfoxides are also irreversibly oxidized to a sulfone metabolite. The reduction of the sulfoxides to sulfide is a nonmicrosomal process and therefore is not a confounding parameter in determining microsomal oxidation. (From Ref. 137.)...

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