Bistoletti M, Alvarez L, Lanusse C, Moreno L
Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN), CONICET, Tandil, Argentina.
J Vet Pharmacol Ther. 2013 Apr;36(2):161-8. doi: 10.1111/j.1365-2885.2012.01401.x. Epub 2012 Apr 26.
An increasing prevalence of roundworm parasites in poultry, particularly in litter-based housing systems, has been reported. However, few anthelmintic drugs are commercially available for use in avian production systems. The anthelmintic efficacy of albendazole (ABZ) in poultry has been demonstrated well. The goal of this work was to characterize the ABZ and metabolites plasma disposition kinetics after treatment with different administration routes in laying hens. Twenty-four laying hens Plymouth Rock Barrada were distributed into three groups and treated with ABZ as follows: intravenously at 10 mg/kg (ABZ i.v.); orally at the same dose (ABZ oral); and in medicated feed at 10 mg/kg·day for 7 days (ABZ feed). Blood samples were taken up to 48 h posttreatment (ABZ i.v. and ABZ oral) and up to 10 days poststart feed medication (ABZ feed). The collected plasma samples were analyzed using high-performance liquid chromatography. ABZ and its albendazole sulphoxide (ABZSO) and ABZSO2 metabolites were recovered in plasma after ABZ i.v. administration. ABZ parent compound showed an initial concentration of 16.4 ± 2.0 μg/mL, being rapidly metabolized into the ABZSO and ABZSO2 metabolites. The ABZSO maximum concentration (Cmax ) (3.10 ± 0.78 μg/mL) was higher than that of ABZSO2 Cmax (0.34 ± 0.05 μg/mL). The area under the concentration vs time curve (AUC) for ABZSO (21.9 ± 3.6 μg·h/mL) was higher than that observed for ABZSO2 and ABZ (7.80 ± 1.02 and 12.0 ± 1.6 μg·h/mL, respectively). The ABZ body clearance (Cl) was 0.88 ± 0.11 L·h/kg with an elimination half-life (T1/2el ) of 3.47 ± 0.73 h. The T1/2el for ABZSO and ABZSO2 were 6.36 ± 1.50 and 5.40 ± 1.90 h, respectively. After ABZ oral administration, low ABZ plasma concentrations were measured between 0.5 and 3 h posttreatment. ABZ was rapidly metabolized to ABZSO (Cmax , 1.71 ± 0.62 μg/mL) and ABZSO2 (Cmax , 0.43 ± 0.04 μg/mL). The metabolite systemic exposure (AUC) values were 18.6 ± 2.0 and 10.6 ± 0.9 μg·h/mL for ABZSO and ABZSO2 , respectively. The half-life values after ABZ oral were similar (5.91 ± 0.60 and 5.57 ± 1.19 h for ABZSO and ABZSO2 , respectively) to those obtained after ABZ i.v. administration. ABZ was not recovered from the bloodstream after ABZ feed administration. AUC values of ABZSO and ABZSO2 were 61.9 and 92.4 μg·h/mL, respectively. The work reported here provides useful information on the pharmacokinetic behavior of ABZ after both i.v. and oral administrations in hens, which is a useful first step to evaluate its potential as an anthelmintic tool for use in poultry.
据报道，家禽体内蛔虫寄生虫的患病率在上升，尤其是在采用垫料饲养系统的鸡舍中。然而，在禽类生产系统中，可用于商业用途的驱虫药很少。阿苯达唑（ABZ）在家禽中的驱虫效果已得到充分证实。这项工作的目的是研究不同给药途径处理后，蛋鸡体内阿苯达唑及其代谢产物的血浆处置动力学。将24只普利茅斯洛克巴拉达蛋鸡分为三组，并用阿苯达唑进行如下处理：静脉注射，剂量为10 mg/kg（ABZ静脉注射）；口服，剂量相同（ABZ口服）；以及在含药饲料中按10 mg/kg·天给药7天（ABZ饲料）。在处理后48小时内（ABZ静脉注射和ABZ口服）以及开始饲料给药后10天内（ABZ饲料）采集血样。使用高效液相色谱法分析采集的血浆样本。静脉注射阿苯达唑后，在血浆中检测到了阿苯达唑及其亚砜（ABZSO）和ABZSO2代谢产物。阿苯达唑母体化合物的初始浓度为16.4±2.0μg/mL，并迅速代谢为ABZSO和ABZSO2代谢产物。ABZSO的最大浓度（Cmax）（3.10±0.78μg/mL）高于ABZSO2的Cmax（0.34±0.05μg/mL）。ABZSO的浓度-时间曲线下面积（AUC）（21.9±3.6μg·h/mL）高于ABZSO2和阿苯达唑的观察值（分别为7.80±1.02和12.0±1.6μg·h/mL）。阿苯达唑的体内清除率（Cl）为0.88±0.11 L·h/kg，消除半衰期（T1/2el）为3.47±0.73小时。ABZSO和ABZSO2的T1/2el分别为6.36±1.50和5.40±1.90小时。口服阿苯达唑后，在处理后0.5至3小时内测得较低的阿苯达唑血浆浓度。阿苯达唑迅速代谢为ABZSO（Cmax，1.71±0.62μg/mL）和ABZSO2（Cmax，0.43±0.04μg/mL）。ABZSO和ABZSO2的代谢产物全身暴露（AUC）值分别为18.6±2.0和10.6±0.9μg·h/mL。口服阿苯达唑后的半衰期值与静脉注射给药后获得的值相似（ABZSO和ABZSO2分别为5.91±0.60和5.57±1.19小时）。饲料给药后，血液中未检测到阿苯达唑。ABZSO和ABZSO2的AUC值分别为61.9和92.4μg·h/mL。本文报道的工作提供了关于母鸡静脉注射和口服阿苯达唑后药代动力学行为的有用信息，这是评估其作为家禽驱虫工具潜力的有用的第一步。
