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oral tramadol in cats was 4.5 hours, suggesting that administration every 12 hours may be appropriate in cats. The plasma concentrations of tramadol and ODM were dose proportional from 0.5 to 4 mg/kg by mouth.(6) The pharmacokinetics of repeated doses of tramadol have not been reported in cats.
ANALGESIC EFFICACY
Acute perioperative pain
In several clinical trials, tramadol has been shown to provide good perioperative analgesic efficacy in dogs. (7-10) However, there is limited published information evaluating the analgesic effect of tramadol using standardized nociceptive stimulation methods in this species. Intravenous tramadol has been shown not
to evoke effective acute cutaneous antinociception
in laboratory Beagle dogs, therefore its use in acute nociceptive pain has been questioned.(11) Oral tramadol administration yielded antinociceptive effects in Greyhounds, but plasma concentrations of tramadol and ODM were lower than expected. Compared with the approved dose (100 mg, PO) in humans, a mean dose
of 9.9 mg/kg, PO resulted in similar tramadol but lower ODM plasma concentrations in Greyhounds.(3) Therefore, more studies of tramadol administration, including studies with larger numbers of dogs and multiple doses, are needed. More comparisons among dog breeds are recommended using the same analytic technique to fully characterize the metabolic pattern of tramadol.
The effects of tramadol on thermal thresholds in cats has been reported. The thermal thresholds exceeded the 95% confidence interval at 0.75, 3, and 6 hours
after 1 mg/kg tramadol, but not at 1, 2, 4, 8, and 24 hours.(12) A dose titration study evaluated the effects of tramadol dosed 0.5 to 4 mg/kg by mouth in cats using a thermal threshold model. Thermal thresholds increased proportionally with increased doses.(6) The duration of increased thresholds were also related to the dose, with 2 mg/kg producing significant effects from less than 6 hours to up to 13 hours after administration, 3 mg/kg producing significant effects from 9 to 12 hours after administration, and 4 mg/kg producing significant effects from 10 to 16 hours after administration.
There are few clinical studies assessing the effects of tramadol administration on cats in controlled clinical trials. A blinded study with negative controls by Brondani et al. 2009 reported the effects of tramadol in patients after ovariohysterectomy.(13) Treatment groups included placebo, the NSAID vedaprofen, tramadol (2 mg/kg
SC), and the combination of tramadol and vedaprofen. Patients were evaluated with a composite pain scale.
All of the patients receiving placebo and vedaprofen received rescue analgesia, 50% of the tramadol patients received rescue analgesia, and none of the vedaprofen and tramadol group received rescue analgesia. The
composite pain scale was significantly lower for the combination of vedaprofen and tramadol from 1 to 56 hours after surgery, but not significantly lower in any of the other treatment groups for more than 1 time point compared with placebo. Another study by Cagnardie
et al. (2011) found that preoperative administration of tramadol (2 mg/kg IV) to cats undergoing gonadectomy decreased the isoflurane requirement and, according
to the pain scoring system used, produced sufficient postoperative analgesia.(14) These findings, together with the positive kinetic behaviour, suggest that 2 mg/kg of tramadol IV might be useful as intra and postoperative analgesic in cats undergoing gonadectomy. A study by Evangelista et al. (2014) compared the analgesic efficacy of preoperative administration of tramadol at two doses (2 mg/kg IM or 4 mg/kg IM) with pethidine (6 mg/kg IM)
in cats undergoing ovariohysterectomy.(15) Tramadol provided adequate analgesia and it was more effective than pethidine to at least six hours for the studied animals. At the higher dose (4 mg/kg IM) tramadol thought to be more effective, as no rescue analgesia was required. Finding from this study were confirmed by Bayldon and Bauquier (2017), who found preoperative administration of oral tramadol (6 mg/kg) or intramuscular tramadol (4 mg/kg) provided effective analgesia for 6 hours following ovariohysterectomy surgery in cats.(16)
Chronic pain
Tramadol is used worldwide for its effects on improved physical function and good tolerability in humans with chronic osteoarthritis pain. Nevertheless, evidence of its efficacy in canine and feline osteoarthritis are scarce. In human pain medicine, tramadol and other serotonin and noradrenalin re-uptake inhibitors (SNRIs) are mainly used for the treatment of chronic pain. It seems probable that the analgesic effect of tramadol in dogs and cats with chronic pain is also likely to be mediated through a non- opioid-based mechanism. This is particularly likely to be the case with any positive analgesic findings in dogs as repetitive tramadol administration in dogs has shown that plasma ODM concentrations decrease by 60% to 70% within just one week.(3) Further investigations on long- term administration of tramadol in chronic pain models
in dogs and cats could help to assess the clinical utility of tramadol in a growing population of geriatric patients with chronic pain.
There are few studies assessing the effects of tramadol administration to clinical canine patients with chronic pain in controlled clinical trials. A blinded study by Malek et al. (2012) investigated the analgesic efficacy or oral tramadol using positive and negative controls, in canine patients with osteoarthritis.(17) Significant improvement was noted in the positive control group (carprofen, 2.2 mg/kg twice a day) and tramadol (4 mg/kg 3 times a day) group compared with the placebo (administered 3 times a day). Plasma concentrations of carprofen and tramadol
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