不同水温条件下恩诺沙星及其代谢物在俄罗斯鲟体内的代谢及消除规律

Metabolism and elimination of enrofloxacin and its metabolites in Acipenser gueldenstaedtii at different water temperature

目的探究12~15℃低水温及18~21℃高水温条件下,恩诺沙星在俄罗斯鲟体内的代谢及消除规律。方法以60 mg/(kg·bw)剂量连续5 d对体重为(750±50)g的健康俄罗斯鲟灌服恩诺沙星,并于停药后1~140 d内连续采集血浆、肌肉、肝脏、肾脏、皮肤及鳃样品,经高效液相色谱-串联质谱法测定其中恩诺沙星及其代谢产物环丙沙星含量,研究连续5 d给药后恩诺沙星及其代谢产物环丙沙星在俄罗斯鲟体内的代谢及消除规律,得出不同温度条件下的休药期。结果在2种水温条件下,恩诺沙星在俄罗斯鲟体内各组织中的达峰时间tmax均为1 d;夏季达峰浓度Cmax小于冬季Cmax;药浓度-时间曲线下总面积AUC随温度升高而增大;药物自体内消除的清除率Clz/f及消除半衰期T1/2z数据均表明,随温度升高药物清除速度加快。恩诺沙星在俄罗斯鲟体内代谢产物为环丙沙星,其消除趋势与恩诺沙星大致相同。结论以皮肤和肌肉作为可食性组织,以恩诺沙星和环丙沙星总量降至0.1 mg/kg为标准,连续5 d以60 mg/(kg·bw)对俄罗斯鲟口灌恩诺沙星后,建议冬季低温条件下休药期为124.2 d,夏季高温条件下休药期为112.9 d。

Objective To explore the pharmacokinetic and elimination of enrofloxacin and its metabolite ciprofloxacin in Acipenser gueldenstaedtii at the low water temperature of 12-15 ℃ and high water temperature of 18-21 ℃. Methods The 60 mg/(kg·bw) dosages were fed by oral administration for the healthy Acipenser gueldenstaedtii weighted(750±50) g for 5 consecutive days. Then the samples of plasma, muscle, liver, kidney, skin and gills were collected during the next 1~140 d, and the content of enrofloxacin and its metabolite ciprofloxacin was determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS). The pharmacokinetic and elimination of enrofloxacin and its metabolite ciprofloxacin in Acipenser gueldenstaedtii were studied after 5 days of continuous administration, and the rest period under different temperature conditions was obtained. Results The tmax of enrofloxacin in Acipenser gueldenstaedtii at the different water temperatures was 1 d. The Cmax in summer was lower than that in winter, and the AUC increased with the increase of temperature. Both the value of Clz/f and T1/2z indicated that the drug clearance rate speeded up with the increase of temperature. The metabolite of enrofloxacin in sturgeon was ciprofloxacin, and the trend of ciprofloxacin was roughly as same as that of enrofloxacin. Conclusion Using skin and muscle as edible tissues, it needs not less than 124.2 d at low temperature in winter and 112.9 d at high temperature in summer before the total amount of enrofloxacin and ciprofloxacin less than 0.1 mg/kg when the enrofloxacin administered at the dose of 60 mg/(kg·bw) for 5 consecutive days to the healthy Acipenser gueldenstaedtii.