Recipient Organization
UNIVERSITY OF TENNESSEE
2621 MORGAN CIR
KNOXVILLE,TN 37996-4540
Performing Department
Small Animal Clinical Sciences
Non Technical Summary
Veterinarians are becoming more aware of the need to manage pain in their reptile patients; however, very little research has been conducted on this subject. Doses of pain relievers used in reptiles, such as opioids and non-steroidal anti-inflammatory drugs (NSAIDs), are arbitrary and based on observations and clinical experiences, not scientific information. A few studies have evaluated the pharmacodynamics of opioids and NSAIDs in reptiles, including our previous study, showing that several opioids and NSAIDs provided antinociception, and therefore most likely pain relief, in bearded dragons. No studies have been published evaluating the pharmacokinetics of opioids or NSAIDs in any reptile. Therefore our proposal is to perform a pharmacokinetic study, i.e. determine blood levels of pain relieving drugs, of four of the drugs we found to provide antinociception in the pharmacodynamic study. The study would evaluate three opioids including morphine at 1 mg/kg IM, butorphanol at 1.5 mg/kg IM, and tramadol at 11 mg/kg PO, and one NSAID, meloxicam at 0.4 mg/kg IM. Blood levels of these drugs would be determined at 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, 24, 36, 48, and 72 hours, in six animals. Findings from this study would allow correlation of blood levels at times when bearded dragons were exposed to an adverse stimulus in the previous study, negating the need to repeat studies with adverse stimuli.Information gained from this study will guide veterinarians in choosing type pain reliever, the dose to administered, and how often it should be administered, to allow better care of their reptile patients.
Animal Health Component
100%
Research Effort Categories
Basic
(N/A)
Applied
100%
Developmental
(N/A)
Goals / Objectives
Hypothesis: Since our previous work showed certain opioids and NSAIDS do provide pain relief to bearded dragons, we believe there should be measurable amounts of these drugs in the bloodstream, and that those levels can be compared to what has been found to be therapeutic in humans. The duration of these drugs in the blood will provide information as to frequency of dosing. Objectives: The objective of this study is to perform a pharmacokinetic study by determining the blood levels of four drugs now known to provide pain relief to bearded dragons. Blood levels of three opioids, morphine at 1 mg/kg IM, butorphanol at 1.5 mg/kg IM, and tramadol at 11 mg/kg PO, and one NSAID, meloxicam at 0.4 mg/kg IM, will be determined by liquid chromotography (HPLC). Blood levels of these drugs would be determined at 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, 24, 36, 48, and 72 hours, in six animals. Levels of drug in bearded dragons will be compared to levels known to be therapeutic in humans, and the duration of measurable levels will be determined.
Project Methods
Analysis will be performed at the University of Tennessee College of Veterinary Medicine using a validated high performance liquid chromatography (HPLC) method developed in our Pharmacology Laboratory (method unpublished). The bioanalytical guidelines of method validation established by the FDA have been and will be followed. This study will evaluate three opioids including morphine at 1 mg/kg IM, butorphanol at 1.5 mg/kg IM, and tramadol at 11 mg/kg PO, and one NSAID, meloxicam at 0.4 mg/kg IM. Blood levels of these drugs will be determined at 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, 24, 36, 48, and 72 hours, in six animals. One animal used in initial studies will be retained as an additional animal in case any of the others cannot be used due to illness or low PCV. One bearded dragon will be purchased prior to the others in order to perform an initial timing study. All proposed time samples (0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours) will be evaluated with all four drugs and any fine tuning of the timing of drawing samples will be performed prior to evaluating the other 6 bearded dragons. A minimum of 6 animals is standard for pharmacokinetic studies. It has been our experience in past pharmacokinetic studies that each species may be slightly different in duration of drug in the bloodstream and it is now our standard practice to completely evaluate all time samples in one animal before continuing the study. At all times no more than 12 samples will be obtained and no more than 10% of the bearded dragon's body weight in blood will be removed in accordance with the University of Tennessee's phlebotomy policy. This policy also states that this maximum cannot be taken any more often than every 2 weeks. As an additional precaution, a PCV and differential will be performed before the study and 2 weeks after each testing period (prior to the next blood draw). If the PCV is below normal for a bearded dragon (17-28%), then testing will be postponed until the PCV, which will be rechecked weekly in this case, reaches normal levels. Most bearded dragons weigh approximately 300 grams, therefore approximately 3 ml can be removed every 2 weeks. The tramadol evaluation will require 0.1 ml of plasma per sample time x 12 = 1.2 ml plasma or 2.4 ml of blood, so sampling can take place during one 2 week time period. Two - 2 week time periods will be needed for the butorphanol evaluation since more plasma is required (butorphanol evaluation will require 0.25 ml of plasma x 12 = 3 ml plasma or 6 ml of blood). The meloxicam and morphine evaluations can be performed on 0.5 ml of plasma, but we will determine if 0.25 ml can be used by evaluating pooled samples before the study begins. If 0.25 ml plasma is used then meloxicam and morphine evaluations will take 4 weeks each to collect blood, but if 0.5 ml of plasma is needed then these evaluations will take 8 weeks each to complete.