Toxciology Brief: Ibuprofen toxicosis in dogs, cats, and ferrets
In humans, ibuprofen taken at standard dosages appears to have a wide margin of safety. In general, there are fewer side effects than with similarly dosed aspirin.1 However, in dogs, cats, and ferrets, ibuprofen has a narrow margin of safety and is a frequent toxicosis reported to the ASPCA Animal Poison Control Center (APCC). In one review of ASPCA APCC data on calls reporting generic drug exposures in dogs and cats, ibuprofen was the most common drug involved.2 Dogs were the animals most commonly poisoned by ibuprofen, and most exposures were acute—usually the result of ingestion of numerous tablets after a dog chewed open a bottle (ASPCA APCC Database: Unpublished data, 2001–2003). Some ibuprofen formulations have a sweet coating and are readily eaten by dogs. In some cases, ibuprofen was administered to pets in the mistaken belief that it was safer than aspirin (ASPCA APCC Database: Unpublished data, 2001–2003).
Mechanism of actionWhile the exact mechanism of ibuprofen's action is not fully understood, it is generally thought that ibuprofen inhibits the conversion of arachidonic acid into various prostaglandins by reversibly blocking the actions of cyclooxygenase (COX) enzymes. By inhibiting COX-2 enzymes, ibuprofen reduces the production of inflammatory mediators such as prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α).3 However, ibuprofen also inhibits COX-1 enzymes, which can reduce the production of substances necessary for maintaining the normal gastric mucosal barriers, renal blood flow, and platelet aggregation.1
About 80% of ibuprofen is absorbed when taken orally in humans1; in dogs, 60% to 86% of the dose is absorbed.4 In humans, the time to reach peak plasma concentrations varies from 47 to 120 minutes, depending on the formulation. Liquid forms reach peak concentrations soonest, chewables next, and tablets last. Ingesting ibuprofen with food decreases the peak plasma concentration and increases the time to reach it.1
Ibuprofen is highly protein-bound (90% to 99%).1 Elimination is through hepatic biotransformation to inactive metabolites excreted by kidney filtration and secretion. About 70% of the drug is excreted in the urine as metabolites or unchanged drug; the rest is lost through feces. Marked enterohepatic recirculation occurs.5 In dogs, the elimination half-life is 3.9 to 5.3 hours.4