Effect of first-pass hepatic metabolism on the disposition of levamisole after intravenous administration in rabbits
Área de conocimiento
Datos de la obra
American journal of veterinary research, 2003, vol. 64, n. 10
American Veterinary Medical Assn.
To evaluate the contribution of first-pass hepatic metabolism of levamisole on levamisole disposition in rabbits. 30 male New Zealand white rabbits. Rabbits were randomly place into 2 groups. Rabbits in the first group received levamisole via the marginal ear vein at the following 3 doses: 12.5, 16, and 20mg/Kg (5 rabbits for each dose). Rabbits of the second group received levamisole via the jejunal vein at the same doses (5 rabbits each). During the following 240 minute period, plasma samples were obtained and quantified for levamisole concentrations by reversed-phase high-performace liquid chromatography. No significant differences were found between pharmacokinetic parameters calculated by compartmental or noncompartmental analysis. Mean hepoatic extraction ratio ranged from 0.044 to 0.017 and from 0.020 to 0.081 when area under the plasma concentration-time curve values were obtained after compartmental or noncompartmental analysis, respectively. After compartmental analysis, plasma concentration decreased bi-exponentially. Mean pharmacokinetic parameter values were as follows for each dose ( 12.5, 16, and 20 mg/Kg, respectively): after levamisole administration via the marginal ear vein, volume of distribution at steady state (Vss)= 4.26, 4.33, and 3.20 L/Kg; total body clearance (Cl) = 49.04,43.77 and 39.26 mL/Kg*min; and half-life associated with β-phase (t,1/2β)= 77.93, 85.39, and 69.79 minutes. After levamisole administration vea the jejunal vein, Vss = 4.38, 2.85, and 2.97 L/Kg, Cl= 48.14, 42.40, and 39.69 mL/Kg*min; and t1/2b = 101.9, 76.71, and 76.13 minutes. Levamisole has a low degree of hepatic extraction in rabbits
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