Effects of concomitant aspirin administration on the pharmacokinetics of indomethacin in man |
| |
Authors: | K C Kwan G O Breault R L Davis B W Lei A W Czerwinski G H Besselaar D E Duggan |
| |
Institution: | (1) Merck, Sharp, and Dohme Research Laboratories, 19486 West Point, Pennsylvania;(2) University of Oklahoma Health Sciences Center, 73106 Oklahoma City, Oklahoma;(3) Present address: G. H. Besselaar Associates, 08540 Princeton, New Jersey;(4) Present address: Veterans Administration Hospital, 19320 Coatsville, Pennsylvania |
| |
Abstract: | Ten healthy volunteers each received single and multiple 50-mg doses of indomethacin orally and a single 25-mg dose of
14
C]indomethacin intravenously in the absence of and concomitantly with 1200 mg of aspirin as a single dose and in a chronic t.i.d. regimen. Systematic analysis of the data resulted in the isolation and quantification of aspirin's effects on the absorption, distribution, biotransformation, excretion, enterohepatic circulation, and accumulation of indomethacin. The effects of chronic aspirin were to suppress the renal clearance, to increase the biliary clearance, to decrease the efficiency of gastrointestinal absorption, and to enhance the enterohepatic circulation of indomethacin. On concomitant administration of 1200 mg of aspirin t.i.d., mean plasma levels of indomethacin were depressed by 20% after a single oral dose, by a smaller margin after multiple oral doses, and not at all after a single intravenous dose of indomethacin. The mean plasma concentration of orally administered indomethacin was decreased by 8% when given concurrently with a single 1200 mg dose of aspirin. Concomitant chronic therapeutic dosages of indomethacin had no effect on salicylate accumulation from repetitive doses of aspirin. |
| |
Keywords: | indomethacin aspirin salicylate interaction absorption biotransformation excretion enterohepatic circulation accumulation effective half-life |
本文献已被 SpringerLink 等数据库收录! |
|