PK/PD evaluations of the novel atypical opioid tapentadol in red-eared slider turtles

The aim of this study was to evaluate the pharmacokinetics and pharmacodynamics of tapentadol (TAP) in red-eared slider turtles after a single intramuscular injection of 5 mg/kg. Turtles (n = 9) were randomly assigned to two treatment groups, according to an open, single-dose, single-treatment, unpaired, two-period crossover design. Group A (n = 5) received a single IM dose of TAP (5 mg/mL) at 5 mg/kg. Group B (n = 4) received a single IM injection of saline (equivalent to the opioid in volume). After a one-month wash-out period, the groups were rotated, and the experiment was repeated. TAP plasma concentrations were evaluated by a validated HPLC-FL method, while an infrared thermal stimulus was applied to the plantar surface of the turtles’ hind limbs to evaluate the thermal withdrawal latency (TWL). TAP plasma concentrations were detectable between 1 and 24 h (2141 – 42 ng/mL, respectively). The TAP-treated group showed a dramatic increase in TWL one hour after drug administration (15.31 ± 4.73 s). Subsequently, TWL decreased with time. Significant differences between the treatment and control groups were apparent up to 10 h following treatment. A linear relationship (r2 = 0.98) between the TAP plasma concentration and effect was found. Given these qualities, TAP appears to be an attractive option for antinociception in turtles because of its rapid onset and acceptable duration of effect. Keywords: opioids, pharmacokinetics, tapentadol, thermal withdrawal latency, turtles