title: Pharmacokinetics and pharmacodynamics of sulfamethoxazole and trimethoprim in swimming crabs (Portunus trituberculatus) and in vitro antibacterial activity against Vibrio: PK/PD of SMZ-TMP in crabs and antibacterial activity against Vibrio.
abstract: Serious bacterial pathogens have recently become a major cause of massive mortality in swimming crabs (Portunus trituberculatus). In this study, the antibacterial activity against Vibrio and the pharmacokinetics (PK) of sulfamethoxazole (SMZ)-trimethoprim (TMP) in crabs were estimated to explore the pharmacokinetics/pharmacodynamics (PK/PD) properties of the SMZ-TMP combination. The in vitro bacteriostatic activity and the anti-Vibrio infection activity of the SMZ-TMP combination at various ratios in crabs were studied. A degree of synergism was observed in the SMZ-TMP combination at ratios ranging from 50:1 to 1:5. The results showed that the MIC50 and MIC90 values for different SMZ-TMP combinations were in the ranges of 0.62-5 and 0.62-10μg/mL, respectively. The distribution of the MIC values of the SMZ-TMP combination at ratios of 1:1 and 5:1 were 0.31-5 and 0.31-10μg/mL, respectively. Crabs were then fed the SMZ-TMP combination (at ratios of 5:1 and 1:1) six successive times and then challenged with Vibrio parahaemolyticus at 1×10(5), 1×10(6), and 5×10(6) colony forming units (cfu) per crab. The results showed that the number of surviving crabs administered SMZ-TMP at a ratio of 1:1 was greater than that of the crabs given SMZ-TMP at a ratio of 5:1. In addition, the tissue distribution and absorption of SMZ-TMP (ratios of 5:1 and 1:1) in crabs were studied through high-performance liquid chromatography (HPLC). In the crabs fed SMZ-TMP at a ratio of 5:1, the CmaxSMZ/TMP values in the hemolymph, hepatopancreas, muscle and gill were 104:1. 0.57:1, 19:1 and 6:1, respectively. In contrast, the corresponding CmaxSMZ/TMP values in these tissues in the crabs fed SMZ-TMP at a ratio of 1:1 were 34:1, 0.14:1, 4:1 and 3:1, respectively. The results showed that TMP was better absorbed and eliminated in the crabs fed SMZ-TMP at a ratio of 1:1 than in the crabs fed this combination at a ratio of 5:1. In addition, TMP was absorbed and eliminated more rapidly in the hepatopancreas than in the gill, muscle and hemolymph. The distribution volume of TMP in the hepatopancreas exceeded that of SMZ observed in the experiments. The results indicated that the PK/PD effect of the SMZ-TMP at a ratio of 1:1 was greater than that of the combination at a ratio of 5:1. Our study suggests that a SMZ-TMP ratio of 1:1 may be used to control bacterial disease in aquatic animals.
authors.affiliation: East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of East China Sea and Oceanic Fishery Resources Exploitation and Utilization, Ministry of Agriculture, Shanghai 200090, China. Electronic address: snow03221@hotmail.com.
authors.forename: Guihong
authors.initials: G
authors.lastname: Fu
authors.affiliation: East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of East China Sea and Oceanic Fishery Resources Exploitation and Utilization, Ministry of Agriculture, Shanghai 200090, China; College of Aquatic and Life, Shanghai Ocean University, Shanghai 201306, China. Electronic address: pjhong2010@163.com.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Peng
authors.affiliation: East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of East China Sea and Oceanic Fishery Resources Exploitation and Utilization, Ministry of Agriculture, Shanghai 200090, China. Electronic address: wy9501@yeah.net.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of East China Sea and Oceanic Fishery Resources Exploitation and Utilization, Ministry of Agriculture, Shanghai 200090, China. Electronic address: zhaoshumyfriend@126.com.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhao
authors.affiliation: East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of East China Sea and Oceanic Fishery Resources Exploitation and Utilization, Ministry of Agriculture, Shanghai 200090, China. Electronic address: fwenhong@163.com.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Fang
authors.affiliation: College of Aquatic and Life, Shanghai Ocean University, Shanghai 201306, China. Electronic address: khu@shou.ecu.cn.
authors.forename: Kun
authors.initials: K
authors.lastname: Hu
authors.affiliation: Zhejiang Institute of Freshwater Fisheries, Huzhou 313001, China. Electronic address: sjinyu@126.com.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Shen
authors.affiliation: Zhejiang Institute of Freshwater Fisheries, Huzhou 313001, China. Electronic address: yaojiayun@126.com.
authors.forename: Jiayun
authors.initials: J
authors.lastname: Yao
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D017756:Aquaculture; D003386:Brachyura / Q000187:drug effects* / Q000382:microbiology; D005260:Female; D006458:Hemolymph / Q000187:drug effects; D008297:Male; D008826:Microbial Sensitivity Tests; D014018:Tissue Distribution; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D014735:Vibrio Infections / Q000517:prevention & control / Q000662:veterinary; D014736:Vibrio parahaemolyticus / Q000187:drug effects* / Q000472:pathogenicity
chemical_list: D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination
keywords: Antibacterial activity; Pharmacokinetics; Sulfamethoxazole (SMZ); Swimming crabs (Portunus trituberculatus); Trimethoprim (TMP); Vibrio