In contrast to humans, tramadol in dogs has a very short half-life (1.7 hr) and negligible amounts of the opioid M1 metabolite are produced.^45–48 Pharmacodynamic studies demonstrate the anesthesia-sparing and pain-modifying effect of parenteral tramadol in dogs.^49–53 Convincing evidence for a pain-modifying effect of oral tramadol, however, remains elusive, and already low plasma levels quickly diminish with sequential administration.^54–57 One small study of oral tramadol did report a statistically significant increase of mechanical threshold levels in dogs, but only at the 5 and 6 hr time points.⁴⁸

In contrast to dogs, cats do produce the μ-agonist M1 metabolite. A pain-modifying effect has been demonstrated in both a thermal threshold and clinical surgical model.^58,59 One case series involving the use of oral tramadol in a flavored compounded form (the drug is otherwise quite bitter), and dose-titration, toxicity, and safety data are currently lacking in both dogs and cats.⁶⁰