Pharmacokinetic and urine profile of tramadol and its major metabolites following oral immediate release capsules administration in dogs

Abstract

The aim of the present paper was to test the oral administration of oral immediate release capsules of tramadol in dogs, to asses both its pharmacokinetic properties and its urine profile. After capsules administration of tramadol (4 mg/kg), involving eight male Beagle dogs, the concentration of tramadol and its main metabolites, M1, M2 and M5, were determined in plasma and urine using an HPLC method. The plasma concentrations of tramadol and metabolites were fitted on the basis of mono- and non-compartmental models, respectively. Tramadol was detected in plasma from 5 min up to 10 h in lesser amounts than M5 and M2, detected at similar concentrations, while M1 was detected in negligible amounts. In the urine, M5 and M1 showed the highest and smallest amount, respectively; M1 and M5 resulted widely conjugate with glucuronic acid. In conclusion, after oral administration of tramadol immediate release capsules, the absorption of the active ingredient was rapid, but its rapid metabolism quickly transformed the parental drug to high levels of M5 and M2, showing an extensive elimination via the kidney. Hence, in the dog, the oral immediate release pharmaceutical formulation of tramadol would have different pharmacokinetic behaviour than in humans.

Comparison of carprofen and tramadol for postoperative analgesia in dogs undergoing enucleation

“…Several studies have examined the pharmacokinetics of oral tramadol in dogs, but these studies were limited to 2 studies in Beagles, 7,32 and one with Greyhounds. 8 These studies measured different metabolites with different methods, so comparison is somewhat difficult, and all three studies revealed a large variation between subjects.…”

“…6 Early research indicated when given orally to dogs, at doses of 4 mg/kg, tramadol achieves therapeutic plasma levels within 5 minutes and persists in plasma at measurable concentrations for between 5 – 10 hours. 7 More recent research showed that at a dose of 10mg/kg given orally to dogs, many of the metabolites thought to be important for opioid-mediated analgesia achieved very low plasma concentrations, suggesting that the reported analgesic effects may be independent of opioid activity. 8 Despite tramadol’s interesting mechanisms, little is published regarding its analgesic efficacy in dogs when given orally for either post-surgical pain or chronic pain.…”

Effects of tramadol and o-desmethyltramadol on canine innate immune system function

“…While pharmacokinetic studies have documented variability in tramadol metabolism between dogs, low plasma concentrations of M1 have been detected in most studies (KuKanich & Papich , ; Giorgi et al. ,b,c,d, ). In addition, M1 has a 400‐fold increased affinity for the μ receptor compared to tramadol in humans (Gillen et al.…”

Tramadol Vs Tapentadol: Anew Horizon in Pain Treatment?

“…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 .…”

“…It is possible therefore that this drug may not provide as effective and safe treatment for pain as in humans (Giorgi et al, 2007;2009a;2009b;2009c;2009d;2010a;2010c;Sousa et al, 2008;Kukanich and Papich, 2011). No stereoselective pharmacokinetic studies on T and its metabolite have been reported in animals to date.…”