Pharmacokinetics of Tramadol and its Metabolites M1, M2 and M5 in Horses Following Intravenous, Immediate Release (Fasted/Fed) and Sustained Release Single Dose Administration

Giorgi, Mario; Soldani, Giulio; Manera, Clementina; Ferrarini, P. L.; Sgorbini, Micaela; Saccomanni, Giuseppe

doi:10.1016/j.jevs.2007.10.004

Cited by 68 publications

(125 citation statements)

References 16 publications

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“…The concentration of tramadol metabolites produced in plasma agrees with previous data (Giorgi et al 2007(Giorgi et al , 2009a, reporting higher production of M2 and M5, than M1 (active metabolite). 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: 91%

“…The maximum value of the CV in intra-/inter-day assay precision for tramadol and its metabolites was 7.5%. As previously reported (Giorgi et al 2007), the analytes were stable at least for 22 weeks if stored at -20 o C.…”

Section: Chromatographysupporting

confidence: 72%

“…Plasma and urine T, M1, M2 and M5 concentrations were evaluated by HPLC fluorimetric detection according to an early method (Giorgi et al 2007). Briefly, the HPLC system was an LC Workstation Prostar (Varian, Walnut Creek, CA, USA) consisting of an LC-10ADvp pump, CTO-10Avp column oven, SCL-10Avp system controller, and RF-10A spectrofluorometric detector.…”

Section: Chromatographymentioning

confidence: 99%

“…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: 91%

Section: Chromatographysupporting

confidence: 72%

Section: Chromatographymentioning

confidence: 99%

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 methods described for the determination of tramadol in biological samples involve gas chromatography (GC) with nitrogen-phosphorous detection [6], flame ionization detection [7] or mass spectrometry (MS) [4,[8][9][10][11][12][13][14][15][16][17]. Methods involving liquid chromatography (LC) with ultraviolet [18][19][20][21], fluorescence [22][23][24][25][26][27][28][29][30][31][32][33], electrochemical [34], diode array [35] or MS detection [36][37][38][39][40] were also reported. However, there is no HPLC-DAD method for determination of tramadol in saliva.…”

Section: Tramadol Hydrochloride (T) (±)-Trans-2-[(dimethyl-amino) Mementioning

confidence: 99%

Development and Validation of High-Performance Liquid Chromatography–Diode Array Detector Method for the Determination of Tramadol in Human Saliva

Aziz¹,

Sayed²,

Mohamed³

et al. 2012

J Chromatograph Separat Techniq

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A high-performance liquid chromatography-diode array detector method (HPLC-DAD) was developed and validated for the determination of tramadol in human saliva. Samples of saliva were prepared utilizing liquid-liquid extraction with hexane-ethyl acetate (4:1, v/v). Propranolol was used as an internal standard (IS). The linear range and average recovery of tramadol were 0.25-4.00 µg/mL and 94.70%, respectively. The intra-and inter-assay precisions at low, intermediate and high concentrations were within 1.40-9.79 % and 0.77-3.98%, respectively. Intra-and inter-assay accuracies were within 98.50-107.13% and 100.44-103.89%, respectively. The proposed method was successfully applied to determine tramadol in saliva concentrations in three healthy volunteers for 24 hours after administration of 100 mg oral doses of tramadol.

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Opioids

Duke‐Novakovski¹

2013

Pain Management in Veterinary Practice

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Pharmacokinetics of Tramadol and its Metabolites M1, M2 and M5 in Horses Following Intravenous, Immediate Release (Fasted/Fed) and Sustained Release Single Dose Administration

Cited by 68 publications

References 16 publications

Pharmacokinetics of tramadol and metabolites after injective administrations in dogs

Pharmacokinetics of tramadol and metabolites after injective administrations in dogs

Development and Validation of High-Performance Liquid Chromatography–Diode Array Detector Method for the Determination of Tramadol in Human Saliva

Opioids

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