Pharmacokinetics and Urine Detection of Tramadol in Adult Horses
ACVIM 2008
A.J. Stewart; D.M. Boothe; C. Cruz-Espindola; E. Baird; J. Springfield
Auburn University College of Veterinary Medicine
Auburn, AL, USA

The purpose was to determine the pharmacokinetic profile of tramadol and metabolites ODT and N-desmethyltramadol (NDT) in serum and urine of adult horses.

Six adult horses (482-564 kg) received intravenous (4.4mg/kg over 3 minutes) and oral (10 mg/kg) tramadol separated by a six-day washout period in a randomized crossover design. Urine and blood samples were collected over 48 hours. Tramadol, ODT, and NDT concentrations were measured using high performance liquid chromatography in serum and urine. Non-compartmental pharmacokinetic analysis was implemented.

Maximum (mean±sd) serum concentration after intravenous tramadol administration for T, ODT and NDT was Cmax[TIV]= 1330±519ng/ml, Cmax[ODTIV]= 0ng/ml and Cmax[NDTIV]= 66.7±20.2ng/ml. The calculated parameters for half-life (t½), volume of distribution (Vd), area under the curve (AUC) and total body clearance (Cl) after intravenous tramadol administration were: t½[TIV]=193±260min; Vd(TIV]=14.3±11.5L/kg, AUC(TIV]=65,234±41,017min*ng/ml and Cl[TIV]=123±143ml/min/kg.

Maximal serum concentration after oral tramadol administration for T, ODT and NDT was Cmax[Toral]=115.1±51.5ng/ml, Cmax[ODToral]=61.1±28.1ng/ml and Cmax[NDToral]= 168±78.7ng/ml. After oral tramadol administration t½[Toral]=74.8±52.8min, t½[ODToral]= 52.3±23.4min, t½[NDToral]=135±45.4min. The oral bioavailability of tramadol was 14.1±10.7%. Concentrations of ODT remained above the minimum reported therapeutic range (for humans >40 ng/ml) for 60-120 minutes in 4 of 6 horses after oral tramadol administration. The relative bioavailability for NDT was 130±123%. Duration of urine detection of T and NDT after oral tramadol administration was 20.3±4.8 and 22±7.8 hrs after oral administration, respectively.

Tramadol has poor oral absorption, but relatively slow clearance in horses compared to other species. Tramadol and NDT can be detected in the urine for approximately 1 day after single dose oral administration.

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Allison Stewart


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