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Effect of first-pass hepatic metabolism on the disposition of levamisole after intravenous administration in rabbits

Villanueva, I.; Diez, M.José.; García, J.J.; Fernández, M.Nélida.; Sahagún, A.M.; Sierra, A.; Sierra, M.

American Journal of Veterinary Research 64(10): 1283-1287

2003


ISSN/ISBN: 0002-9645
PMID: 14596467
DOI: 10.2460/ajvr.2003.64.1283
Accession: 003728451

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Objective--To evaluate the contribution of first-pass hepatic metabolism of levamisole on levamisole disposition in rabbits. Animals--30 male New Zealand White rabbits. Procedures--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 min; and half-life associated with b-phase (t1/2b) = 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 min; and t1/2b = 101.9, 76.71, and 76.13 minutes. Conclusions--Levamisole has a low degree of hepatic extraction in rabbits. Reprinted by permission of the publisher.

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