The influence of urinary pH on the disposition of indomethacin in healthy volunteers.

The influence of urinary pH on the plasma levels and renal elimination of unchanged indomethacin has been studied in seven healthy volunteers with the use of a specific and sensitive gas-liquid chromatographic method assay for indomethacin in plasma and urine. There is a wide variation in the terminal t1/2 (2.5-10.3 h) and the AUC (5264-12693 ng/ml h) of indomethacin after a standard oral dose (50 mg) under 'normal' urinary condition. Such variation is probably, in part, due to an intersubject difference in extrarenal elimination of the drug. The urinary recovery of unchanged indomethacin is highest at alkaline pH (15.7 +/- 5.3%), lowest at acidic pH (3.5 +/- 2.0%) and the 'normal' value is 7.1 +/- 1.6%. These differences are statistically significant. Despite such influence there is no apparent change in plasma levels of the drug under uncontrolled and controlled (acidic and alkaline) conditions of urinary pH. The clinical implication is that possible changes in urinary pH during long-term treatment of arthritic patients may not affect the overall kinetics of indomethacin which is extensively eliminated by the extrarenal route.