PHARMACOKINETIC/PHARMACODYNAMIC ASSESSMENTS OF 10 MG/KG TRAMADOL INTRAMUSCULAR INJECTION IN YELLOW-BELLIED SLIDER TURTLES (TRACHEMYS SCRIPTA SCRIPTA).

In reptiles, administration of opioid drugs has yielded unexpected results with respect to analgesia. The aims of this study were to assess the pharmacokinetic/pharmacodynamic (PK/PD) properties of tramadol and its active metabolite M1 and to evaluate the effect of the renal-portal system on the PK/PD parameters in yellow-bellied slider turtles. Turtles (n = 19) were randomly assigned to four treatment groups, according to a masked, single-dose, four-treatment, unpaired, four-period crossover design. Group A (n = 5) received a single IM dose of tramadol (50 mg/mL) at 10 mg/kg in the proximal hind-limb. Group B (n = 5) received the same IM dose but in the fore-limb. Group C (n = 5) and D (n = 4) received a single IM injection of saline (NaCl 0.9 %) of equivalent volume to the volumes of tramadol injected in the hind- and fore-limb, respectively. Groups were rotated (1 month washout period) until the completion of the cross over study. Tramadol plasma concentrations were evaluated by a validated HPLC-FL method. An infrared thermal stimuli was applied to the plantar surface of the turtles’ hind-limbs to evaluate the thermal withdrawal latency (TWL). The two PK profiles of tramadol differed in the first 2 h following administration, but overlapped in the limination phases. The metabolite M1 was formed in both the treatment groups, showing similar pharmacokinetic trends, although the amount of M1 was significantly higher (20 %) in the hind-limb vs fore-limb group. Turtles given tramadol in the hind- and fore-limb showed a significant increase in TWL over the periods of 0.5-48 and 8-48 h, respectively. The calculated % maximal possible response (% MPR) was low (about 24 %). The PK/PD correlations between M1 plasma concentrations vs % MPR appeared to show a counter clockwise hysteresis loop shape.