RT Journal Article
SR Electronic
T1 Effects of sodium salicylate on elimination kinetics of indomethacin and bile production in dogs.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 962
OP 967
VO 18
IS 6
A1 W S Beck
A1 K Dietzel
A1 G Geisslinger
A1 H Engler
A1 H Vergin
A1 K Brune
YR 1990
UL http://dmd.aspetjournals.org/content/18/6/962.abstract
AB We investigated the effects of sodium salicylate on the elimination kinetics of indomethacin in bile duct-cannulated beagles. Indomethacin and metabolites were quantified by HPLC in plasma, bile, and urine. Indomethacin was administered as iv bolus injection and iv infusion to yield a steady-state plasma concentration of approximately 1 microgram/ml. Following sodium salicylate, given either iv (25 mg/kg) or via duodenal fistula (50 mg/kg), the indomethacin plasma level dropped instantaneously by 60-70%. Concomitantly, total systemic clearance from the plasma and biliary clearance were increased significantly. In addition, a reduced plasma protein binding of indomethacin and a significant increase in the volume of distribution were observed. The amount of indomethacin, excreted as free and conjugated drug in bile, was significantly increased temporarily by sodium salicylate. The total amount eliminated in bile (approximately 70% of the dose), however, was not changed by sodium salicylate co-administration. The bile flow was significantly enhanced for at least 4 hr. Both phase 1 metabolism and renal excretion of indomethacin remained practically unaffected by sodium salicylate treatment.