Pharmacokinetics of tramadol, and its metabolite <i>O</i>‐desmethyl‐tramadol, in cats

Pypendop, Bruno H.; Ilkiw, Jan E.

doi:10.1111/j.1365-2885.2007.00921.x

Cited by 124 publications

(109 citation statements)

References 19 publications

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“…The low concentration of M1 is in accordance with previous data in dogs (Kukanich and Papich 2004, McMillan et al 2008, Giorgi et al 2009a, horses (Giorgi et al 2007, Shilo et al 2008), goats (de Sousa et al 2008 and donkeys (Giorgi et al 2007) suggesting that in these species the effectiveness of tramadol might be lower than in cats (Pypendop and Ilkiw 2008) and humans (Grond and Sablotzki 2004).…”

Section: Discussionsupporting

confidence: 80%

“…A potential clinical advantage of tramadol is the absence of adverse effects common to other analgesics, such as opioid derivatives and non steroidal anti-inflammatory drugs (NSAIDs), which suggests that tramadol may be useful for long term therapy in chronic pain in animals. Tramadol appears to be more rapidly degraded to inactive metabolites, in goats (de Sousa et al 2008), dogs (Kukanich and Papich 2004, McMillan et al 2008, Giorgi et al 2009a, donkeys (Giorgi et al 2009c) and horses (Giorgi et al 2007, Shilo et al 2008) than in cats (Pypendop and Ilkiw 2008) and humans (Grond and Sablotzki 2004), which may affect the efficacy and safety of tramadol in these species. The aim of the present study was to test the bioavailability of tramadol administered by intramuscular (IM) and intravenous (IV) routes, assessing the absolute bioavailability of the drug.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of tramadol and metabolites after injective administrations in dogs

Giorgi

Carlo²,

Łebkowska‐Wieruszewska³

et al. 2010

Polish Journal of Veterinary Sciences

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The aim of this study was to determine the pharmacokinetics of tramadol and its main metabolites after IV and IM injections. The pharmacokinetic cross-over study was carried out on 6 healthy male beagle dogs. Tramadol was administered by intravenous (IV) and intramuscular (IM) injection at 4 mg/kg. Tramadol and its main metabolites O-desmethyl-tramadol (M1), N-,N-didesmethyl-tramadol (M2) and N-,O-didesmethyl-tramadol (M5) concentrations were measured in plasma samples by a HPLC coupled with fluorimetric detection; pharmacokinetic evaluations were carried out with a compartmental and non-compartmental model for tramadol and its metabolites, respectively. The bioavailability of the drug, ranging between 84-102% (mean 92%), was within the generally accepted values for a positive bioequivalence decision of (80-125%). After the IM injection the mean plasma drug concentration peak was reached after a Tmax of 0.34 h with a Cmax of 2.52 μg/mL. No therapeutic relevant differences were observed between IM and IV administration. The minimal effective plasma concentration was reached after a few minutes and maintained for about 6-7 h in both administrations. M1 plasma concentration was low and the amounts of the other metabolites produced were analogous in both routes of administration. In conclusion, tramadol was rapidly and almost completely absorbed after IM administration and its systemic availability was equivalent to the IV injection. The different onset time and duration of action observed were very small and probably therapeutically irrelevant. The IM injection is a useful alternative to IV injection in the dog.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of tramadol and metabolites after injective administrations in dogs

Giorgi

Carlo²,

Łebkowska‐Wieruszewska³

et al. 2010

Polish Journal of Veterinary Sciences

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“…com. 15, 30, 60, e CLINIC AND SURGERY Schroder et al receptors (PYPENDOP & ILKIW, 2008). Nonetheless, the primary metabolite O-demethyl-tramadol (M1) is 2 to 4 times more potent than the parent drug and may account for part of the analgesic effect.…”

Section: Introductionmentioning

confidence: 99%

Effects of tramadol and acepromazine on intraocular pressure and pupil diameter in young healthy cats

et al. 2018

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This study aimed to investigate the effects of the systemic administration of acepromazine, tramadol and the association of both on intraocular pressure (IOP) and pupil diameter (PD) in young healthy cats. Cats were randomly allocated into three groups (n=10/each) and intramuscular acepromazine (AG), tramadol (TG) or acepromazine combined with tramadol (ATG) were injected. PD (electronic caliper) and IOP (applanation tonometry) were assessed before (baseline) and following 15, 30, 60, and 120 minutes of treatments. It was verified that in AG, PD decreased significantly from time point 30 to 120 (P=0.002), but such reduction did not differ significantly from baseline (P=0.89). In TG, PD increased significantly from the first 15 minutes, until the last time point of evaluation (P<0.001). In ATG, PD increased significantly from time point 30 to 120 when compared to baseline (P<0.001); but significant differences from time point 30 to 120 were not seen (P=0.71). Comparisons among groups showed that PD values of TG and ATG were significantly higher than that of AG (P<0.05). IOP values, on the other hand, did not change significantly among time points and groups (P>0.05). It can be concluded that tramadol alone or in association with acepromazine produced significant mydriasis for up to 120 minutes, without changing IOP values in normal cats. Results of this study suggested that tramadol alone or in association with acepromazine caused significant mydriasis and did not change IOP values in normal cats. Therefore, it may be considered a satisfactory pre-anesthetic combination for ophthalmic surgery in cats. However, further studies are warranted on the use of such protocols in cats with ophthalmic diseases undergoing ocular or intraocular surgery.

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“…Although it has been used for some time now, our understanding and ability to predict the time course of its pharmacological effects in animals are still hampered by the presence of active metabolites and the coexistence of opioid and non-opioid mechanisms. Recently, T has been reported to be metabolized faster to inactive metabolites N-desmethyl tramadol (M2) and O,N-didesmethyl tramadol (M5), in goats (Sousa et al, 2008), dogs (McMillan et al, 2008;Giorgi et al, 2009a;2009b;2009c;2009d;2010a;Kukanich and Papich, 2011), horses (Giorgi et al, 2007;Shilo et al, 2008;Cox et al, 2010;Giorgi et al, 2010b), llamas , alpacas (Giorgi et al, 2010c), peafowl (Black et al, 2010), hawks than in cats (Pypendop and Ilkiw, 2008). The use of T has also been suggested for zoo animals .…”

Section: Tramadolmentioning

confidence: 99%

Tramadol Vs Tapentadol: Anew Horizon in Pain Treatment?

Giorgi¹

2012

American Journal of Animal and Veterinary Sciences

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Problem statement: Acute and chronic pain is a common presenting sign in animal species and human beings. Approach: Classical opioids provide very effective pain relief, although they may be less effective in the treatment of chronic pain due to their limited therapeutic windows and the induced opioid receptor down regulation. Atypical opioids, such as tramadol and tapentadol, have a dual mechanism of action and have been designed to overcome these issues through an opiate-sparing effect. Results: Tramadol activates mu opioid receptors and in addition, inhibits serotonin and noradrenalin reuptake. These actions are the result of the different enantiomers and tend to be reliant on their metabolism. Indeed, the O-desmethyltramadol phase I metabolite, is 200-300 times more potent for mu opioid receptor activation than the parental compound. For these reasons, the drug's effectiveness can vary among subjects. In veterinary medicine its effectiveness, especially after oral administration, is still uncertain and controversial. Tapentadol is a novel, atypical opioid with a unique mechanism of action. It was launched on the European drug market at the end of 2011. It has been proposed as the first representative of a new pharmacological class of centrally acting analgesics, namely, the mu opioid receptor agonist, noradrenalin reuptake inhibitors. The first human studies describe this molecule as safe and effective (equianalgesic to morphine). The drug has great potential for veterinary use because it exists as a single enantiomer only, it does not require metabolic activation to be effective and adverse effects triggered by the serotonin reuptake inhibition action are negligible. Conclusion/Recommendations: For these reasons, TAP is a promising compound however at this stage, more investigation is required before it can be recommended for regular use in veterinary medicine, the possibility of undesirable effects is yet to be entirely excluded.

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Pharmacokinetics of tramadol, and its metabolite O‐desmethyl‐tramadol, in cats

Cited by 124 publications

References 19 publications

Pharmacokinetics of tramadol and metabolites after injective administrations in dogs

Pharmacokinetics of tramadol and metabolites after injective administrations in dogs

Effects of tramadol and acepromazine on intraocular pressure and pupil diameter in young healthy cats

Tramadol Vs Tapentadol: Anew Horizon in Pain Treatment?

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