Intra-arterial pharmacokinetics and pulmonary first-pass of levamisole in rabbits
Área de conocimiento
Datos de la obra
Pharmacological research, 2002, vol. 45, n. 4
The pharmacokinetics of levamisole after intra-arterial administration of 12.5, 16 and 20 mg kg−1 was investigated in rabbits. After compartmental analysis, the disposition of levamisole was well described by a two-compartment open model with mean values ± SD of: = 0.1650 ± 0.0839, 0.1611 ± 0.0298, 0.2312 ± 0.0540 min−1, and = 0.0118 ± 0.0022, 0.0125 ± 0.0026, 0.0120 ± 0.0024 min−1, for the three doses studied, respectively. There were no doserelated differences (one-way analyses of variance (ANOVA), P 0.05) in , , total body clearance (Cl) and volume of distribution at steady state (Vss). The AUC increased significantly with the doses (249.7, 376.7 and 562.5 μg min ml−1). After non-compartmental analysis there were no significant differences in plasma elimination rate constant ( ), MRT and Vss as a function of dose, but these differences were significant for Cl, between 16 and 20 mg kg−1, and AUC (one-way ANOVA, P 0.05). The two-way ANOVA showed no significant differences between the values obtained for the three doses when – , Cl, Vss and Va were compared while AUC showed significant changes. On the other hand, the pharmacokinetic analysis (compartmental and non-compartmental) showed significant differences in AUC, Cl, Vss and Va, but there were no significant differences when – were compared. The slow clearance of levamisole by rabbit lung compared to a high pulmonary blood flow rate makes the possibility of significant first-pass lung metabolism unlikely in this animal species.