The aim of the present study is to evaluate the pharmacokinetics of T and its major metabolites M1, M2 and M5 after the single oral administration of an SR tablet and rectal suppositories in dogs (4-6 mg·kg⁻¹ m.c.). The plasma concentration data after SR-tablet and rectal administration were fitted on the basis of a mono- and non-compartmental model, respectively. T plasma concentration after SR tablet administration was quantitatively detected in three dogs, M1 was quantized in only one dog while M2 and M5 were quantized in all the dogs. T showed median values of Cmax, Tmax and T₁/₂ of 40 (20-170) ng·mL⁻¹, 3 (4-2) and 1.88 (2.21-1.44) hours, respectively. M5 showed median values of Cmax, Tmax and T₁/₂ of 0.1 (90-190) ng·mL⁻¹, 2 (3-1) and 4.23 (6.58-1.85) hours, respectively. M2 showed median values of Cmax, Tmax and T₁/₂ of 220 (80-330) ng·mL⁻¹, 4 (7-3) and 4.49 (6.39-1.57) hours, respectively. Following rectal administration, T was detected from 5 minutes up to 10 h in a smaller amount than M5 and M2. T median value of Cmax was 140 ± 60 ng·mL⁻¹ in 0.56 ± 0.41 h (Tmax). K₀₁ t₁/₂ and K₁₀ t₁/₂ were 0.27 ± 0.25 h and 2.24 ± 1.82 h, respectively. M1 was detectable from 5 min up to 2 h, showing low values (7-28 ng·mL⁻¹). The present findings suggest oral SR tablet and suppository rectal formulation have similar pharmacokinetic behavior and would not have suitable pharmacokinetic characteristics to be administered once-a-day as an effective and safe treatment for pain in dogs.
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