氟苯尼考在三疣梭子蟹(Portunus trituberculatus)疾病模型内的代谢动力学

为了解健康和疾病条件下药物在三疣梭子蟹(Portunus trituberculatus)体内的代谢差异,在构建三疣梭子蟹溶藻弧菌疾病模型的基础上,按25mg/kg剂量分别给健康和患病三疣梭子蟹单次口灌氟苯尼考后,采用高效液相色谱法测定了其肝胰腺、肌肉和血浆中的药物浓度,药时数据应用3P97药代动力学软件拟合。结果显示:氟苯尼考在健康和患病条件下三疣梭子蟹相同组织中的药时曲线形态相似,三种组织的药时数据均符合带时滞的一级吸收二室开放模型;肝胰腺吸收药物最快,肌肉次之,血浆最慢;与健康组相比,患病蟹肝胰腺、肌肉、血浆三种组织对氟苯尼考的吸收和消除速度明显减慢,达峰时间推迟,半衰期延长,清除率减低,最高药物浓度下降,表观分布容积和药时曲线下总面积变大。说明疾病使氟苯尼考在三疣梭子蟹体内的吸收、分布、代谢和消除均发生了显著变化,建议患病三疣梭子蟹口服氟苯尼考的休药期至少10d。

PHARMACOKINETICS OF FLORFENICOL IN DISEASE MODEL OF PORTUNUS TRITUBERCULATUS

To understand the metabolic differences of florfenicol in healthy and diseased Portunus trituberculatus, the pharmacokinetics of florfenicol were investigated based on Vibrio alginolyticus disease model. P. trituberculatus was orally administered in a single dose of 25 mg/kg in water temperature (21±2)°C. Tissues of haemolymph, muscle, and hepatopancreas were sampled and measured using high performance liquid chromatography (HPLC). Results show that florfenicol in healthy P. trituberculatus have a similar concentration-time curve with that of diseased animals. The profiles of the three tissues could be described by a two-compartment open model with a time lag. Florfenicol can be distributed unevenly in all tissues, absorbed most quickly in hepatopancreas and most slowly in plasma. Compared with the healthy P. trituberculatus, the rate of absorption and elimination in diseased P. trituberculatus slowed, the peak time delayed and half-liveextended, clean-up ratio and maximum drug concentration decreased, apparent volume of distribution and the area under the curve increased. These pharrnacokinetic parameters showed that florfenicol in diseased P. trituberculatus changed greatly in absorption, distribution, elimination, and metabolism. According to the maximum residue limit (MRL) of 0.1 mg/kg in tissues, the withdrawal period should not be less than 10 days under experiment condition.