Recipient Organization
UNIVERSITY OF TENNESSEE
2621 MORGAN CIR
KNOXVILLE,TN 37996-4540
Performing Department
Comparative Mecidine
Non Technical Summary
Tramadol has been used routinely for the relief of moderate to severe pain in humans for years, but there is little information regarding the use of this drug in birds. This study will evaluate the metabolism, analgesic properties and duration of action of tramadol in Hispaniolan Amazon parrots, and will determine the most effective dose. Tramadol holds the promise of being the first orally administered long-acting, analgesic with numerous mechanisms of action.
Animal Health Component
100%
Research Effort Categories
Basic
(N/A)
Applied
100%
Developmental
(N/A)
Goals / Objectives
Understanding and treating painful conditions in animals has gained considerable and deserved attention in recent years. It is now the standard of practice to provide pain relief to animals under conditions considered painful in humans, and the Institute of Laboratory Animal Resources guide mandates pain relief in all vertebrate animals. Several recent advances in avian analgesia have supported the clinical application of analgesic drugs for the avian patient. The goal of this project is to determine a therapeutic dose of tramadol for use in parrots. Phase I: This phase of the study is descriptive, not hypothesis driven, and will determine the pharmacokinetics of tramadol HCl in Hispaniolan Amazon parrots. This portion of the study will be performed at the University of Tennessee College of Veterinary Medicine. OBJECTIVES: To determine the pharmacokinetics of tramadol and its active metabolite M1 following three dosages (5 mg/kg PO, 11 mg/kg PO and 5 mg/kg IV) in Hispaniolan Amazon parrots (Amazona ventralis). EXPECTED OUTPUT: HPLC will be used to evaluate plasma levels of tramadol and its metabolites after dosing. These levels will be correlated with evidence of analgesia determine in phase II of the study. Phase II: Oral administration of tramadol HCl will provide analgesia for greater than 4 hours, the maximum length of analgesia associated with butorphanol administration, in Hispaniolan Amazon parrots. This portion of the study will be performed at the University of Wisconsin School of Veterinary Medicine. OBJECTIVES: To evaluate the antinociceptive effect and duration of action of tramadol HCl after oral administration in Hispaniolan Amazon parrots. Two oral dosages of tramadol HCl (5 mg/kg and 11 mg/kg) and a control vehicle-only (Ora-Sol SF) treatment will be evaluated in a dose-response study using withdrawal threshold latency to a noxious thermal stimulus. EXPECTED OUTCOME: We will determine what dose of tramadol provides analgesia and the length of drug efficacy. These results will be correlated with plasma drug levels to determine plasma levels associated with analgesia in parrots.
Project Methods
Pharmacokinetic study: Six adult Hispaniolan Amazon parrots (3 male, 3 female) determined to be healthy based on results of history, physical examination, complete blood count and plasma biochemistry panel will be used. Animals will be removed from the UTCVM Laboratory Animal Care facility 12-24 hours prior to dosing for acclimation to temporary study facilities. Tramadol (5 mg/kg) will be administered IV slowly over 1 minute into the medial metatarsal vein. Blood (0.25 mL) will be collected from the jugular vein or other peripheral vessel at specific time points (determined in the pilot portion of the study) following tramadol administration. Sample handling will be as described in the pilot study. Animals will be returned to the Laboratory Animal Care facility after sample collection is complete. There will be a 3-4 week washout period. The procedures described previously will be repeated for each of the oral doses (5 mg/kg and 11 mg/kg), except that birds will be fasted for 3 hours prior to dosing. Oral medication will be placed into the crop with a metal gavage feeding tube. The pharmacokinetics of two different oral doses of tramadol are being examined so we can determine if metabolism is linear and also to compare plasma levels with analgesic effects observed in Phase II. This portion of the study will be performed at the University of Tennesee College of Veterinary Medicine. Pharmacodynamic Study: The analgesic effect of tramadol HCl will be evaluated using 2 dosages (5 mg/kg PO and 11 mg/kg PO) and a control vehicle-only group using a masked, within-subjects, cross-over experimental design. Analgesic efficacy will be evaluated in parrots (n=15) exposed to a thermal stimulus, and foot withdrawal thresholds using a custom designed analgesimetry perch that has been employed in previously published studies in parrots. The test box is constructed to evaluate analgesia in awake perching birds. Details of the testing method have been previously described. Briefly, the box is constructed of acrylic plastic and the perch is designed to deliver a thermal stimulus to one foot. The birds will be observed remotely via a video camera and music will be played at all times to minimize introduction of extraneous visual and auditory clues. Parrots are placed in the test box three times for two-hour acclimation periods in the week prior to testing. The final acclimation period is 24 hours prior to testing. This portion of the study will be performed at the University of Wisconsin School of Veterinary Medicine. Based on these two portions of the study, a therapeutic dose of tramadol will be determined for Hispaniolan Amazon parrots.