Pharmacokinetic evaluation of tramadol and its major metabolites after single oral sustained tablet administration in the dog: a pilot study

The study evaluated the pharmacokinetics of tramadol and its major metabolites O-desmethyltramadol (M1), N-desmethyltramadol (M2) and N–O didesmethyltramadol (M5) following a single oral administration of a sustained release (SR) 100 mg tablet to dogs. Plasma tramadol concentration was greater than the limit of quantification (LOQ) in three dogs, M1 was quantified only in one dog while M2 and M5 were quantified in all of the dogs. The median values of Cmax (maximum plasma concentration), Tmax (time to maximum plasma concentration) and T1/2 (half-life) for tramadol were 0.04 (0.17–0.02) μg mL−1, 3 (4–2) and 1.88 (2.211–1.435) h, respectively. M5 showed median values of Cmax, Tmax and T1/2 of 0.1 (0.19–0.09) μg mL−1, 2 (3–1) and 4.230 (6.583–1.847) h, respectively. M2 showed median values of Cmax, Tmax and T1/2 of 0.22 (0.330–0.080) μg mL−1, 4 (7–3) and 4.487 (6.395–1.563) h, respectively. The findings suggest that the SR formulation of tramadol may not have suitable pharmacokinetic characteristics to be administered once-a-day as an effective and safe treatment for pain in the dog.