Pharmacokinetics and Safety of Acetaminophen in Adult Horses
Mercer, Melissa Ann
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Due to the detrimental side effects of NSAID administration, such as gastrointestinal ulceration and renal papillary necrosis, there is a profound need for clinical pain relief in horses with long term orthopedic disease whereby gastrointestinal side effects are obviated. Acetaminophen is one of the most commonly used analgesic drugs in humans, and is readily available as an inexpensive generic over-the-counter preparation. Acetaminophen has a number of mechanisms of action that differ from NSAIDs, including actions on the serotonergic, opioid, endocannabinoid and lipoxygenase pathways. These alternate pathways may provide greater efficacy against chronic or neuropathic pain in equine patients. Acetaminophen was preferred by physicians over COX-2 and nonselective NSAIDs, even when those drugs were coupled with proton-pump inhibitors to reduce gastrointestinal side effects; due to cost considerations and the occurrence of adverse side effects from those drugs. In horses, acetaminophen has been reported to be efficacious as an adjunct treatment for laminitis in one pony, and was an effective analgesic agent when combined with NSAIDs in a model of inducible foot pain. However, no studies have been performed to validate a dose-response curve in horses. A study recently completed by our group demonstrated rapid absorption following oral administration of acetaminophen. Reported human therapeutic plasma concentrations were achieved within 30 minutes of administration, with no clinical or clinicopathologic evidence of adverse side effects after two weeks of repeated dosing. Dose simulation trials indicate that a change in dosage schedule may be required in order to provide adequate plasma concentrations.
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