Opioids are considered the most effective drugs for controlling pain in mammals, but in reptiles, opioid drug administration has yielded unexpected results with respect to analgesia (1–3). Tapentadol (TAP) is a novel atypical opioid drug labeled for human use. It has shown in humans an equivalent analgesic activity than that of morphine, and a reduction in the rate of adverse effects. If the reduction in adverse effects observed in humans holds true in reptiles, TAP could be an attractive analgesic option. The aim of this study was to evaluate the pharmacokinetics and the pharmacodynamics of TAP in yellow-bellied slider, after a single intramuscular injection of 5 mg kg 1. Turtles (n = 9) were randomly assigned to two treatment groups, according to a single-dose, single-treatment, unpaired, two-period crossover design. Group A (n = 5) received a single IM (proximal front limb) dose of TAP (5 mg ml 1) at 5 mg kg 1. Group B (n = 4) received a single IM injection of saline (equivalent volume to opioid volumes) of TAP at the same site. After a 1-month washout period, groups were rotated and the experiment repeated. Blood samples (1 ml) were collected from the subcarapacial venipuncture site at 0, 1, 2, 4, 6, 10, and 24, h and TAP plasma concentrations determined by a validated HPLC-FL method. At the same time of the blood collections an infrared thermal stimuli (70°C) was applied to the plantar surface of the turtles’ hind limbs to evaluate the thermal withdrawal latency (TWL). The thermal antinociceptive effect was expressed as Maximum Possible Response (% MPR). TAP plasma concentrations were detectable between 1 and 24 h (1619–37 ng ml 1, respectively). The TAP treated group showed an increase in TWL 1 h after drug administration (13.32 6.40 s). Subsequently, TWL decreased with time, significant differences between treatment and control groups were apparent up to 10 h following treatment. Mean MPR increased to a maximum of 46.68 12.30% at 1 h and decreased to a minimum of 1.62 2.77% at 24 h. The MPR difference between TAP and saline group was significant up to 10 h. A linear relationship (r2 = 0.99) between TAP plasma concentration and effect was found. Given these findings, TAP appears to be an attractive option for antinociception in turtles, due to its rapid onset and acceptable duration of effect.
PK/PD EVALUATION OF THE NOVEL ATYPICAL OPIOID TAPENTADOL IN YELLOW-BELLIED SLIDER TURTLES (TRACHEMYS SCRIPTA SCRIPTA)
GIORGI, MARIO;
2015-01-01
Abstract
Opioids are considered the most effective drugs for controlling pain in mammals, but in reptiles, opioid drug administration has yielded unexpected results with respect to analgesia (1–3). Tapentadol (TAP) is a novel atypical opioid drug labeled for human use. It has shown in humans an equivalent analgesic activity than that of morphine, and a reduction in the rate of adverse effects. If the reduction in adverse effects observed in humans holds true in reptiles, TAP could be an attractive analgesic option. The aim of this study was to evaluate the pharmacokinetics and the pharmacodynamics of TAP in yellow-bellied slider, after a single intramuscular injection of 5 mg kg 1. Turtles (n = 9) were randomly assigned to two treatment groups, according to a single-dose, single-treatment, unpaired, two-period crossover design. Group A (n = 5) received a single IM (proximal front limb) dose of TAP (5 mg ml 1) at 5 mg kg 1. Group B (n = 4) received a single IM injection of saline (equivalent volume to opioid volumes) of TAP at the same site. After a 1-month washout period, groups were rotated and the experiment repeated. Blood samples (1 ml) were collected from the subcarapacial venipuncture site at 0, 1, 2, 4, 6, 10, and 24, h and TAP plasma concentrations determined by a validated HPLC-FL method. At the same time of the blood collections an infrared thermal stimuli (70°C) was applied to the plantar surface of the turtles’ hind limbs to evaluate the thermal withdrawal latency (TWL). The thermal antinociceptive effect was expressed as Maximum Possible Response (% MPR). TAP plasma concentrations were detectable between 1 and 24 h (1619–37 ng ml 1, respectively). The TAP treated group showed an increase in TWL 1 h after drug administration (13.32 6.40 s). Subsequently, TWL decreased with time, significant differences between treatment and control groups were apparent up to 10 h following treatment. Mean MPR increased to a maximum of 46.68 12.30% at 1 h and decreased to a minimum of 1.62 2.77% at 24 h. The MPR difference between TAP and saline group was significant up to 10 h. A linear relationship (r2 = 0.99) between TAP plasma concentration and effect was found. Given these findings, TAP appears to be an attractive option for antinociception in turtles, due to its rapid onset and acceptable duration of effect.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
