复方磺胺嘧啶口灌给药在拟穴青蟹(Scylla paramamosain)体内药动学和组织分布与消除

Pharmacokinetics, Tissue Distribution and Elimination of Sulfadiazine and Trimethoprim in Mud Crab (Scylla paramamosain) After Oral Administration

研究了水温为(27±1)℃、盐度为10条件下,单剂量(100 mg/kg)口灌给药复方磺胺嘧啶(磺胺嘧啶SD∶甲氧苄啶TMP=5∶1)后,SD和TMP在拟穴青蟹(Scylla paramamosain)体内的药动学以及在肌肉、肝胰腺和鳃组织中的分布和消除规律。结果显示,拟穴青蟹口灌复方磺胺嘧啶后,血淋巴中SD和TMP药物浓度-时间关系曲线均符合一级吸收二室模型,SD和TMP的峰浓度(C_(max))分别为49.56 mg/L和2.79 mg/L,药时曲线下面积(AUC)分别为1417.6 mg/L·h和82.7 mg/L·h;肝胰腺是SD和TMP峰浓度最高的组织,其C_(max)分别为59.36 mg/kg和74.82 mg/kg。由此可见,大量TMP蓄积在肝胰腺中,进入血液循环的TMP很少。在鳃组织中,SD和TMP的C_(max)分别为51.89 mg/kg和42.58 mg/kg,消除半衰期分别为23.28 h和25.29 h;鳃组织中药物浓度比较高,且消除速度较快,推测其在药物代谢中承担着消除功能。在肌肉中,SD和TMP的C_(max)分别为44.95 mg/kg和10.09 mg/kg,消除半衰期分别为25.09 h和35.08 h。以0.1 mg/kg和0.05 mg/kg分别为SD和TMP的最高残留限量(MRL),95%置信区间,推算SD和TMP在拟穴青蟹肌肉中的理论休药期分别为290.6 h和302.8 h,在肝胰腺中分别为340.4 h和377.0 h。

The pharmacokinetics, tissue distribution and elimination of sulfadiazine （SD） and trimethoprim （TMP） in mud crab （Scylla paramamosain） were investigated in order to provide scientific data to support its safe use. SD and TMP were orally administrated at a single dose of SD （83.3 mg/kg） and TMP （16.7 mg/kg） at temperature of （27±1） ℃ and seawater salinity of 10. The hemolymph concentration-time curve for SD and TMP were described by a two-compartment model with first order absorption. Peak hemolymph concentration （Cmax） for SD and TMP was 49.56 mg/L and 2.79 mg/L, respectively, and area under curve （AUC） for SD and TMP was 1417.6 mg/L·h and 82.7 mg/L·h, respectively. Of the tissues analyzed, the hepatopancreas was the tissue with the highest SD and TMP concentrations, and Cmax was 59.36 mg/kg and 74.82 mg/kg, respectively. Thus, a large amount of TMP was accumulated in the hepatopancreas, while only a small amount of TMP entered blood circulation. In gill, peak concentration for SD and TMP was 51.89 mg/kg and 42.58 mg/kg, respectively, and elimination half-life was 23.28 h and 25.29 h, respectively. The drug concentration in gill tissue was relatively high and the elimination rate was fast, suggesting crab gill plays a role in drug elimination. In muscle, peak concentration for SD and TMP was 44.95 mg/kg and 10.09 mg/kg, respectively, and elimination half-life was 25.09 h and 35.08 h, respectively. According to SD and TMP elimination and the maximum residue limit of 0.1 mg/kg for SD and 0.05 mg/kg for TMP, the theoretical withdrawal time of SD/TMP in muscle and hepatopancreas, was 290.6 h/302.8 h and 340.4 h/377.0 h, respectively.