盐酸氯苯胍药饵给药条件下在异育银鲫体内药动学和组织分布与消除规律

Pharmacokinetics,tissue distribution and elimination of robenidine hydrochloride in Carassius auratus gibelio after oral administration via medicated feed

研究了水温(25±1)℃条件下,盐酸氯苯胍(robenidine hydrochloride,ROBH)以20 mg·kg^(-1)单剂量拌饲药饵给药后在异育银鲫(Carassius auratus gibelio)体内药动学及在肝胰脏、肌肉、喉、肾脏、肠、鳃、脑和胆汁中的分布和消除规律。结果显示,药饵给药后异育银鲫血浆中盐酸氯苯胍的药时数据符合一级吸收二室模型,血药达峰时间T_(max)为4 h,血药浓度峰值C_(max)为1.117 mg·L^(-1),药时曲线下面积(AUC_(0-∞))为68.39 mg·L^(-1)·h,消除半衰期(t_(1/2β))为56.86 h。盐酸氯苯胍在异育银鲫组织中分布较广,C_(max)大小依次为:肠、肾脏、肝胰脏、胆汁、鳃、喉、脑和肌肉;AUC_(0-∞)大小依次:肠、肾脏、胆汁、肝胰脏、喉、鳃、脑和肌肉。异育银鲫摄食药饵后,盐酸氯苯胍通过肠道吸收进入肝胰脏,经血液循环广泛分布于各组织器官中,最后主要从肾脏排出,这也与其较大的V_d值相印证。研究还发现,粘孢子虫感染异育银鲫的喉、鳃和脑等组织均有盐酸氯苯胍分布,为该病的治疗提供了理论依据。若以10μg·kg^(-1)为肌肉中最高残留限量,在本实验条件下,建议休药期不少于15 d。

The pharmacokinetics,distribution and elimination of robenidine hydrochloride（ ROBH） in silver crucian carp,Carassius auratus gibelio were investigated after oral administration at 20 mg·kg-1 body weight via medicated feed at water temperature of（ 25 ± 1） ℃. ROBH concentrations in plasma and tissues were determined by HPLC method. The results showed that the plasma ROBH concentration-time of silver crucian carp could be best described by a two-compartment model with first-order absorption. The peak time（ Tmax）was 4 h,and the maximum concentration（ Cmax） was 1. 117 mg·L-1,the area under the concentration-time curve（ AUC0-∞） was 68. 39 mg·L-1·h,and the elimination hal-life（ t1/2β） of plasma was 56. 86 h. ROBH showed a wide distribution in tissues of Carassius auratus gibelio. ROBH concentration,Cmaxin tissues in sequence from high to low was intestine,kidney,hepatopancreas,gallbladder,gill,throat,brain and muscle; AUC0-∞in tissues in sequence from high to low was intestine,kidney,gallbladder,hepatopancreas,throat,gill,brain and muscle. After ROBH-medicated feed were fed by silver crucian carp,robenidine hydrochloride was absorbed by intestine and entered into hepatopancreas,distributed to various tissues and organs via blood circulation,and then excreted mainly by the kidney,which was confirmed by the larger Vd value. It was observed that ROBH could distribute into throat,gill and brain,which myxosporidia could infect. If the maximum residue limits（ MRL） in muscle was 10 μg·kg-1,the withdraw period should not be less than 15 days under this experimental condition.