3种磺胺类药物在中国对虾(Fenneropenaeus chinensis)体内的药代动力学特征

Pharmacokinetics of Three Sulfa-Drugs in the Fenneropenaeus chinensis

关键词:  磺胺二甲嘧啶  磺胺嘧啶  磺胺对甲氧嘧啶  中国对虾  药代动力学

Key words:  SM2  SD  SMD  Fenneropenaeus chinensis  Pharmacokinetics

摘要:

采用高效液相色谱法研究了3种磺胺类药物在中国对虾体内的药物代谢动力学特征，这3种磺胺类药物包括磺胺二甲嘧啶(SM2)、磺胺嘧啶(SD)及磺胺对甲氧嘧啶(SMD)。实验期间，中国对虾的养殖水温为(24.6±2.4)℃，单次口服3种磺胺类药物的剂量均为100 mg/kg。结果显示，3种磺胺类药物在中国对虾体内的血药经时过程均符合一级吸收二室开放模型，SM2的主要药动学参数T1/2β、AUC、Vd、CL、Tmax、Cmax分别为25.812 h、34.066 mg/L•h、94.553 L/kg、2.608 L/h•kg、2 h、1.07 mg/L；SD的主要药动学参数T1/2β、AUC、Vd、CL、Tmax、Cmax分别为46.446 h、45.39 mg/L•h、97.207 L/kg、1.504 L/h•kg、1 h、1.17 mg/L；SMD的主要药动学参数T1/2β、AUC、Vd、CL、Tmax、Cmax分别为66.296 h、65.917 mg/L•h、40.015 L/kg、0.763 L/h•kg、2 h、2.00 mg/L。结果表明，SMD在中国对虾体内分布比SM2、SD更广泛；中国对虾体内SM2的消除相半衰期最短，SD次之，SMD消除相半衰期最长；3种磺胺类药物在中国对虾体内72 h药物吸收量SMD最高，SD次之，SM2最低；且SMD药物清除率最低，SD次之，SM2药物清除率最高，所以口服3种磺胺类药物72 h中国对虾体内SMD残留最多，SD次之，SM2残留最少。SMD在中国对虾体内药效更加持久，故在不考虑使用成本及毒副作用等其他因素的前提下，比较这3种磺胺类药物的药物代谢动力学特征，更加推荐使用SMD。

Abstract:

To better understand the use of sulfa drugs in aquaculture, especially in the culture of Fenneropenaeus chinensis, we studied the pharmacokinetics of three sulfa drugs in F chinensis using the high performance liquid chromatography (HPLC). The three selected sulfa drugs were sulfadimidine (SM2), sulfamethoxydiazine (SMD) and sulfadiazine (SD). The water temperature for the experiment was (24.6±2.4)℃. Healthy shrimp received oral administration of the drugs at a dose of 100 mg/kg. The results showed that the hemolymph concentration-time course of SM2, SMD and SD conformed to a two-compartment open model with the first order absorption after oral administration. Major pharmacokinetic parameters such as T1/2β, AUC, Vd, CL, Tmax and Cmax were 25.812 h, 34.066 mg/L•h, 94.553 L/kg, 2.608 L/h•kg, 2 h, 1.07 mg/L respectively for SM2, and 46.446 h, 45.39 mg/L•h, 97.207 L/kg, 1.504 L/h•kg, 1 h, 1.17 mg/L for SD, and 66.296 h, 65.917 mg/L•h, 40.015 L/kg, 0.763 L/h•kg, 2 h, 2.00 mg/L for SMD. These suggested that SMD was more widely distributed and absorbed than SM2 and SD in F. chinensis. The elimination half-life showed the order of SM2SD>SM2. As for the drug clearance rate, SMD had the fastest rate and SM2 had the slowest rate. Therefore in 72 hours after the oral administration, SMD had the most residues and the SM2 had the least residues in F. chinensis. In another word, SMD had the longest-lasting pesticide effect. Taking no account of other factors such as the cost and side effects, SMD could be the most suitable sulfa drug according to its pharmacokinetic characteristics. The comparison of the elimination half-life showed that SMD had the most enduring efficacy.