Effects of zomepirac and indomethacin on renal blood flow and electrolyte excretion in anesthetized monkeys |
| |
Authors: | Grant K Moore Byron Noordewier Jerry B Hook Karl A Yorgey Patrick J ONeill |
| |
Institution: | 1. Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA;2. Department of Drug Metabolism, McNeil Pharmaceutical, Spring House, PA 19477, USA |
| |
Abstract: | Zomepirac sodium is a new inhibitor of prostaglandin cyclooxygenase with an potency equivalent to indomethacin. Since inhibitors of prostaglandin synthesis have marked effects on renal hemodynamics, zomepirac may be expected to reduce renal blood flow (RBF) in a manner similar to indomethacin. This study compares the effects of zomepirac and indomethacin on RBF and electrolyte excretion in anesthetized Rhesus monkeys. Each experiment consisted of a control period followed by 3 or 4 drug treatment periods in which increasing doses of zomepirac (0.5 to 20 mg/kg) or indomethacin (0.5 to 10 mg/kg were given. Indomethacin (5 mg/kg) reduced RBF by 22% and the higher dose (10 mg/kg) reduced RBF by an additional 13%. Zomepirac had little effect on RBF in doses as high as 20 mg/kg. At any given dose the mean plasma concentration of zomepirac was equal to or greater than indomethacin. Peak indomethacin concentration was 48 μg/ml after the 10 mg/kg dose while the peak zomepirac, after 20 mg/kg, was 158 μg/ml. Neither drug had a significant effect on either glomerular filtration rate or excretion rate of sodium or potassium. Thus, zomepirac had only minimal effects on RBF while indomethacin decreased RBF of anesthetized monkeys in a manner qualitatively similar to its effect in other species. The minimal renal effects caused by zomepirac relative to indomethacin in this primate may indicate a therapeutic advantage for zomepirac in man. |
| |
Keywords: | Reprint requests should be sent to B N at present adress: Department of Pharmacology University of North Dakota Grand Forks ND 58202 |
本文献已被 ScienceDirect 等数据库收录! |
|