Transdermal fentanyl combined with nonsteroidal anti-inflammatory drugs for analgesia in horses

This study investigated the pharmcokinetics, efficacy, and safety of the fentanyl transdermal therapeutic system (TTS) in horses in which there was an inadequate analgesic response to nonsteroidal anti-inflammatory drugs (NSAIDs) alone. Nine horses with pain that was refractory to therapeutic doses of phenylbutazone (n = 3) or flunixin meglumine (n = 6) subsequently also received between 39 and 110 microg/kg of transdermal fentanyl. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 60, and 72 hours after patch application, and a radioimmunoassay was used to determine serum fentanyl concentrations. Pharmacokinetic values were determined by noncompartmental analysis. Physical examination findings were recorded in all horses, and pain and lameness grading systems were used to assign scores to 8 and 6 horses, respectively. All horses tolerated the administration of fentanyl TTS, in that no clinically significant adverse effects attributable to fentanyl were observed. Use of the TTS resulted in variable serum concentrations of fentanyl, with a peak serum concentration of 2.2+/-1.1 ng/mL (mean+/-SD) and a time to peak serum concentration of 26+/-13 hours. After transdermal fentanyl administration, mean time to reach serum fentanyl concentrations consistent with analgesia in other species (1 ng/mL) was 14 hours. In addition, serum fentanyl concentrations of 1 ng/mL or greater were maintained in all but one horse for at least 18 hours. Pain scores were significantly decreased after fentanyl TTS and NSAID administration (P < .05), but lameness scores were not significantly different (P > .05). Overall, administration of fentanyl TTS had a favorable pharmacokinetic profile in horses with clinical pain, and the fentanyl TTS in combination with NSAIDs appeared to provide safe and effective analgesia in most of the horses with pain that was refractory to NSAID therapy alone.