Pharmacokinetics of tramadol and its major conjugates after a single per os administration of a sustained tablet and per rectum suppositories formulations in dogs

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 C max, T max and T 1/2of 40 (20-170) ng-mL -1, 3 (4-2) and 1.88 (2.21-1.44) hours, respectively. M5 showed median values of C max, T max and T 1/2 of 0.1 (90-190) ng-mL -1, 2 (3-1) and 4.23 (6.58-1.85) hours, respectively. M2 showed median1 values of C max, T max and T 1/2 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 C max was 140 ± 60 ng-mL -1 in 0.56 ± 0.41 h (T max). K 01 t 1/2 and K 10t 1/2 were 0.27 ± 0.25 h and 2.24 ± 1.82 h, respectively. Ml 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.