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本文对鲫以15 mg/kg·bw的剂量单次口灌甲砜霉素进行药物动力学参数模拟研究,以15 mg/kg·bw的剂量连续口灌给药3 d进行药物残留研究。结果表明甲砜霉素的药—时曲线均较符合有吸收一室开放模型,10℃水温条件下甲砜霉素在鲫体内的主要药物动力学参数为:吸收半衰期(t1/2ka)4.63 h;峰浓度(Cmax)5.71μg/m L;达峰时间(Tmax)10.94 h;消除半衰期(t1/2β)13.68 h;表观分布容积(Vd/F)1.53 L/kg;清除率(CLb)0.08 L/(h·kg);药时曲线下面积(AUC)195.99μg·h/m L。25℃水温条件下甲砜霉素在鲫体内的药物动力学参数为:吸收半衰期(t1/2ka)2.72 h;峰浓度(Cmax)5.60μg/m L;达峰时间(Tmax)6.98 h;消除半衰期(t1/2β)9.87 h;表观分布容积(Vd/F)1.6 4L/kg;清除率(CLb)0.12 L/(h·kg);药时曲线下面积(AUC)130.16μg·h/m L。不同水温条件下甲砜霉素在鲫鱼各组织中的代谢明显不同,表现为水温升高甲砜霉素消除则加快,水温降低甲砜霉素消除则变慢。结果还显示在两个温度下,甲砜霉素在鲫鱼主要组织中消除均较慢,在给药72h后,仍可在在皮肤、肌肉、肾脏组织中检测到甲砜霉素。同时,皮肤中的药物代谢速率相对于其他组织较慢,因此,建议把皮肤作为甲砜霉素药物残留的靶组织。若以15 mg/kg·bw的剂量连续口灌给药甲砜霉素后,建议甲砜霉素在鲫鱼体内的休药期定为:在10℃至少为10d,在25℃至少为6 d。
In this paper, the pharmacokinetic parameters of thiamphenicol were orally administered to the crucian carp at a dose of 15 mg / kg · bw for 15 days. The drug residue was continuously dredged for 3 days at a dose of 15 mg / kg · bw. The results showed that the drug-time curve of thiamphenicol was in line with the one-compartment open model. The main pharmacokinetic parameters of thiamphenicol in crucian carp at 10 ℃ were: half-life (t1 / 2ka) 4.63 h ; Peak concentration (Cmax) 5.71 μg / m L; peak time (Tmax) 10.94 h; elimination half-life 13.68 h; apparent volume of distribution (Vd / F) 1.53 L / kg; 0.08 L / (h · kg), and the area under the curve (AUC) 195.99 μg · h / m L. The pharmacokinetic parameters of thiamphenicol in crucian carp at 25 ℃ were as follows: half-life (t1 / 2ka) 2.72 h, peak concentration 5.60 μg / m L, peak time 6.98 h, The half-life (t1 / 2β) was 9.87 h, the apparent volume of distribution (Vd / F) was 1.6 4L / kg and the clearance rate was 0.12 L / (h · kg) m L. The metabolism of thiamphenicol in different tissues of crucian carp was significantly different under different water temperature conditions, which showed that the increase of water temperature accelerated the elimination of thiamphenicol and the decrease of water temperature reduced thiamphenicol. The results also showed that thiamphenicol was slowly eliminated in the main tissues of crucian carp at both temperatures, and thiamphenicol was still detected in the skin, muscle and kidney tissues 72 h after administration. At the same time, the rate of drug metabolism in the skin is relatively slow compared to other tissues, therefore, it is recommended to use the skin as the target tissue for residual thiamphenicol drugs. After continuous oral administration of thiamphenicol at a dose of 15 mg / kg · bw, it is recommended that the withdrawal duration of thiamphenicol in crucian carp be at least 10 days at 10 ° C and at least 6 days at 25 ° C .