Renal handling of zomepirac sodium (McN-2783-21-98) in the rat.
The plasma and renal clearance of zomepirac, a weak organic acid, was investigated in anesthetized CR Wistar rats after administration of single bolus i.v. injections or continuous i.v. infusions of the 14C-labeled compound. Adjustment of urine pH to the alkaline range caused more than an 8-fold lowering of the plasma elimination half-life (from 7.0 to 0.8 hr) and enhanced renal clearance by a factor of 53 compared to control. Acidification of the urine or probenecid administration increased the elimination half-life (to 10.9 and 17.5 hr, respectively), and decreased renal and plasma clearance of zomepirac. Since zomepirac is highly bound to plasma proteins (approximately 98%), only a small fraction of the drug is available for filtration at the glomerulus. Therefore, the renal elimination of zomepirac is accomplished mainly by active tubular secretion. Passive nonionic reabsorption is a major factor in determining the net clearance of the drug.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000378:metabolism*; D002723:Chlorobenzoates / Q000097:blood / Q000378:metabolism*; D004347:Drug Interactions; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D011339:Probenecid / Q000494:pharmacology; D011758:Pyrroles / Q000378:metabolism*; D051381:Rats; D014046:Tolmetin / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D014556:Urine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002723:Chlorobenzoates; D011758:Pyrroles; C020549:zomepirac; D014046:Tolmetin; D011339:Probenecid