1142 AJVR, Vol 73, No. 8, August 2012 A nalgesia is becoming increasingly important in avi- an medicine, and controlling pain is a vital compo- nent in improving the well-being of companion birds and birds kept in captive settings. Recognition of the signs of pain in birds can be difficult because of spe- cies differences, and careful observation by owners or animal caretakers is needed to recognize changes in be- havior that might be associated with pain. 1–3 Numerous analgesic medications have been exam- ined in birds; however, butorphanol tartrate and nal- Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis) Marcy J. Souza, DVM, MPH; David Sanchez-Migallon Guzman, LV, MS; Joanne R. Paul-Murphy, DVM; Sherry K. Cox, PhD Objective—To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals—9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Procedures—Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from –5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were col- lected from –5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentra- tions of tramadol and its major metabolites were measured via high-performance liquid chromatography. Results—Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administra- tion of tramadol at a dose of 10 mg/kg were < 40 ng/mL for the entire time period, but oral administration at a dose of 30 mg/kg resulted in mean plasma concentrations > 100 ng/ mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Conclusions and Clinical Relevance—Oral administration of tramadol at a dose of 30 mg/ kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analge- sia in Hispaniolan Amazon parrots. (Am J Vet Res 2012;73:1142–1147) buphine hydrochloride are currently the opioid medi- cations of choice for pain management in psittacine species. 4–10 Unfortunately, these 2 medications are ad- ministered by injection and have a short duration of ac- tion. An analgesic medication that can be administered orally and that has a longer duration of action would be ideal for pain management in birds. Tramadol is a weak, centrally acting μ-opioid re- ceptor agonist and also has action at κ- and δ-opioid re- ceptors. 11 The main metabolite, O-desmethyltramadol (ie, M1), has greater activity at μ-opioid receptors than Received January 13, 2011. Accepted August 2, 2011. From the Department of Comparative Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (Souza, Cox); and the Department of Veterinary Medicine and Epidemiol- ogy, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (Sanchez-Migallon Guzman, Paul-Murphy). Supported by the Morris Animal Foundation (grant No. D09ZO-308). The authors thank Lillian Gerhardt and Nancy Zagaya for assistance with sample collection and Jason Yarbrough for assistance with sample analysis. Address correspondence to Dr. Souza (msouza@utk.edu). ABBREVIATIONS AUC Area under the plasma concentration–time curve AUC 0–∞ Area under the plasma concentration–time curve from time 0 to infinity AUMC Area under the first moment time curve Cmax Maximum plasma concentration F Systemic oral bioavailability Tmax Time to maximum plasma concentration