恩诺沙星及其代谢产物环丙沙星在牙鲆体内代谢消除规律

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in flounder Paralichthys olivaceus

以80 mg/kg鱼体重对牙鲆单次口灌给药恩诺沙星,给药后在不同的时间点取样,用高效液相色谱荧光检测器检测,研究恩诺沙星及其主要代谢产物环丙沙星在牙鲆体内的代谢消除规律。研究表明,停药后0.25 h,肌肉中恩诺沙星残留量最低。各组织的消除半衰期依次为腮>肝脏>血液>肾脏>肌肉,其中肌肉中恩诺沙星消除半衰期最低为67.759 h,消除最快,停药后12 d检测不到恩诺沙星。停药后0.25 h,在牙鲆血液、肝脏、肾脏中均有环丙沙星残留,残留量依次为肝脏>肾脏>血液,肌肉和鳃中未检出环丙沙星。停药后22 d在血液、肝脏和肾脏3个组织中仍然能够检测出恩诺沙星,但是停药7 d后这3个组织中均检测不出环丙沙星。结果显示,恩诺沙星在牙鲆体内代谢速度较慢,而且只是在一段时间内有脱乙基代谢为环丙沙星的反应发生,但并不是在恩诺沙星消除的全过程都发生,而且代谢物环丙沙星在牙鲆体内的消除速度要比恩诺沙星快。

In this study we investigated the pharmacokinetics and elimination of enrofloxacin （ENRO） and its metabolite ciprofloxacin （CIP） in Paralichthys olivaceus. After the oral administration of a single dose at 80 mg/kg ~ bw, the time courses of concentrations of ENRO and CIP in fish tissues were measured with high-performance liquid chromatography and a fluorescence detector. At 0. 25 h, the muscle retained the lowest level of ENRO residues among five tissues （See below）. The elimination half-life of ENRO in the five tissues was in the order： gills 〉 liver 〉 kidney 〉 blood 〉 muscle. ENRO in muscle was eliminated fastest and had the lowest elimination half-life of 67. 759 h;hence in the 12th day after the drug withdrawal, ENRO in the muscle was no longer detectable. At 0. 25 h, the concentration of CIP residues in different tissues was in the order： liver 〉 kidney 〉 blood, while CIP could not be detected in the muscle and gills at the same time. In blood, liver and kidney, ENRO was still detectable in the 22nd day after the drug withdrawal; whereas CIP could not be detec- ted in these tissues since the 7tb day. These results indicated that the metabolism and elimination of ENRO in P. olivaceus was relatively slow. We also found that the degradation of ENRO into CIP occurred only in a short period after the ENRO administration. Obviously the elimination of CIP in flounder was much faster than that of ENRO.