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Pharmacokinetics of hydrocodone and tramadol administered for control of postoperative pain in dogs following tibial plateau leveling osteotomy

Marian E. Benitez DVM, MS1, James K. Roush DVM, MS2, Butch KuKanich DVM, PhD3, and Rose McMurphy DVM4
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  • 1 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.
  • | 2 Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.
  • | 3 Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.
  • | 4 Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

Abstract

OBJECTIVE To evaluate the pharmacokinetics of hydrocodone (delivered in combination with acetaminophen) and tramadol in dogs undergoing tibial plateau leveling osteotomy (TPLO).

ANIMALS 50 client-owned dogs.

PROCEDURES Dogs were randomly assigned to receive tramadol hydrochloride (5 to 7 mg/kg, PO, q 8 h; tramadol group) or hydrocodone bitartrate–acetaminophen (0.5 to 0.6 mg of hydrocodone/kg, PO, q 8 h; hydrocodone group) following TPLO with standard anesthetic and surgical protocols. Blood samples were collected for pharmacokinetic analysis of study drugs and their metabolites over an 8-hour period beginning after the second dose of the study medication.

RESULTS The terminal half-life, maximum serum concentration, and time to maximum serum concentration for tramadol following naïve pooled modeling were 1.56 hours, 155.6 ng/mL, and 3.90 hours, respectively. Serum concentrations of the tramadol metabolite O-desmethyltramadol (M1) were low. For hydrocodone, maximum serum concentration determined by naïve pooled modeling was 7.90 ng/mL, and time to maximum serum concentration was 3.47 hours. The terminal half-life for hydrocodone was 15.85 hours, but was likely influenced by delayed drug absorption in some dogs and may not have been a robust estimate. Serum concentrations of hydromorphone were low.

CONCLUSIONS AND CLINICAL RELEVANCE The pharmacokinetics of tramadol and metabolites were similar to those in previous studies. Serum tramadol concentrations varied widely, and concentrations of the active M1 metabolite were low. Metabolism of hydrocodone to hydromorphone in dogs was poor. Further study is warranted to assess variables that affect metabolism and efficacy of these drugs in dogs.

Contributor Notes

Address correspondence to Dr. Benitez (marian.benitez19@gmail.com).