The interaction between indomethacin and probenecid. A clinical and pharmacokinetic study.
The interaction between indomethacin and probenecid has been studied in 17 patients with rheumatoid arthritis with the use of a specific gas-liquid chromatographic method for the assay of indomethacin in plasma and urine. Probenecid in a dose of 0.5 gm twice daily improved the therapeutic response to indomethacin administered in a dose of 25 mg 3 times daily for a 3-wk period. There was an increase in the mean AUC of indomethacin in plasma from 2,553 +/- 213 hr ng/ml to 4,181 +/- 384 hr ng/ml when probenecid was given, but there was no change in the plasma half-life of indomethacin. There was a reduction in the mean plasma clearance of indomethacin from 174 +/- 21 ml/kg/hr to 107 +/- 14 ml/kg/hr when probenecid was added to the indomethacin therapy and a decrease in the apparent volume of distribution from 0,927 +/- 0.16 L/kg to 0.613 +/- 0.13 L/kg. There was no change in the amount of free indomethacin excreted in the urine during probenecid therapy but there was a reduction in the urinary excretion of free plus glucuronide conjugate of indomethacin from 8,967 +/- 867 microgram/day to 4,760 +/- 674 microgram/day, with a fall in the mean renal clearance of indomethacin glucuronide from 271 +/- 48 ml/min to 126 +/- 57.0 ml/min. The changes in the plasma indomethacin concentration profile during probenecid therapy are due to a decrease in the nonrenal clearance of indomethacin possibly because of reduced biliary clearance.
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006207:Half-Life; D006801:Humans; D007213:Indomethacin / Q000378:metabolism* / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011339:Probenecid / Q000378:metabolism* / Q000627:therapeutic use; D011485:Protein Binding
D001798:Blood Proteins; D011339:Probenecid; D007213:Indomethacin