Effect of first-pass hepatic metabolism on the disposition of levamisole after intravenous administration in rabbits.
OBJECTIVE
To evaluate the contribution of first-pass hepatic metabolism of levamisole on levamisole disposition in rabbits.


METHODS
30 male New Zealand White rabbits.


METHODS
Rabbits were randomly placed into 2 groups. Rabbits in the first group received levamisole via the marginal ear vein at the following 3 doses: 12.5, 16, and 20 mg/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-performance liquid chromatography.


RESULTS
No significant differences were found between pharmacokinetic parameters calculated by compartmental or noncompartmental analysis. Mean hepatic 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 (CI) = 49.04, 43.77, and 39.26 mL/kg x min; and half-life associated with beta-phase (t1/2beta) = 77.93, 85.39, and 69.79 minutes. After levamisole administration via the jejunal vein, Vss = 4.38, 2.85, and 2.97 L/kg; CI = 48.14, 42.40, and 39.69 mL/kg x min; and t1/2b = 101.9, 76.71, and 76.13 minutes.


CONCLUSIONS
Levamisole has a low degree of hepatic extraction in rabbits.
Villanueva
Irma
I
Pharmacology Area, Department of Pharmacology, Toxicology, Nursing and Physical Therapy, Veterinary Faculty, University of Leon, 24071 León, Spain.
Diez
M José
MJ
García
Juan J
JJ
Fernández
M Nélida
MN
Sahagún
Ana M
AM
Sierra
Ana
A
Sierra
Matilde
M
D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D007978:Levamisole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D011817:Rabbits
D000871:Anthelmintics; D007978:Levamisole