Pharmacokinetics Of Marbofloxacin And Florfenicol In Penaeus Japonicus

This study consists of three parts,the in vitro antibacterial activities and post-antibiotic effects of marbofloxacin and florfenicol against the major marine pathogenic Vibrio were investigated and the important role of the post-antibiotic effect played in the aquacultural drug applications was also discussed in the first part.The second part clarified the differences of pharmacokinetics between intramuscular and oral administration to Penaeus japonicus and discussed the rational dosage regimen after combining the minimal inhibitory concentration and post-antibiotic effect with pharmacokinetic parameters. The third part clarified the differences of pharmacokinetics of florfenicol between intrasinusly and orally administration in kuruma shrimp, Penaeus japonicus under the conditions of submerged and not-submerged sand and the kinetic characteristics in hemolymph, muscle and liver.Then The minimal inhibitory concentration,post-antibiotic effect and pharmacokinetic parameters were combined to discuss the rational dosage regimen.The susceptibilities and the Minimal inhibitory concentrations (MICs) and Minimum bactericidal concentrations (MBCs) of marbofloxacin and florfenicol against Vibrio alginolyticus, Vibrio harveyi, Vibrio fischeri and Vibrio splendidus were spectively determined by means of oxford cup and twofold dilution,and compared with those of other three antimicrobial agents including difloxacin,enrofloxacin and norfloxacin; the postantibiotic effects(PAE) of marbofloxacin and florfenicol against Vibrio alginolyticus, Vibrio harveyi and Vibrio splendidus were determined by colony counting.The results showed that the activity of marbofloxacin against the four marine pathogenic Vibrios was similar to that of florfenicol, but more potent than those of difloxacin,enrofloxacin and norfloxacin. It was shown that, at the concentrations of 1MIC,2MIC and 4MIC, the PAE of marbofloxacin and florfenicol against Vibrio alginolyticus, Vibrio harveyi and Vibrio splendidus was 0.49h,0.87h,1.17h and 0.39h,0.46h,1.07h;0.64h,0.98h and 1.22h,0.48h,0.70h,1.12h;0.75h,1.02h and 1.25h,0.63h,1.03h,1.19h,respectively. This showed that the PAE of marbofloxacin against Vibrio alginolyticus, Vibrio harveyi and Vibrio splendidus was very significant. And the PAE will be higher when the concentrations were increased.The pharmacokinetics of intrasinusly, intramuscularly and orally administered marbofloxacin were determined in kuruma shrimp, Penaeus japonicus at water temperatures of 25±0.6℃. Following intramuscular and oral administration, the plasma concentration-time data for enrofloxacin were best described as a two-compartment open model with first-order absorption and elimination, the pharmacokinetic equation:Cim=15.521e-1.153t+7.90e-0.059t-23.421 e-11.73t and Cpo= 17.486e-0.399t+3.01e-0.051t-20.496 e-0.408t, respectively. After intramuscular and oral administration, the main pharmacokinetic parameters were as follows:t1/2Ka 0.059and 1.697, tmax0.25h and 2.0h, t1/2α0.601h and 2.103h, Cmax20.7858μg/mL and 12.4774μg/mL, F 99.56% and 94.18%, t1/2β11.769h and 13.535h, respectively. It indicated more quickly absorption, wider distribution,higher peak plasma concentration, higher bioavailability and faster elimination by intramuscular administration than by oral administration.In this study,pharmacokinetic parameters and the postantibiotic effect (PAE) and the minimum inhibitory concentration (MIC) combine to discuss the dosage regimen of Marbofloxacin.The scheme of Marbofloxacin was established to shrimp bacterial disease, at the intervals of 13.6 hours and 11.8 hours, with the dose of 14.30mg/kg and 19.17 mg/kg by intramuscular and oral administration, respectively.The pharmacokinetics of intrasinusly and orally administered florfenicol was determined in kuruma shrimp, Penaeus japonicus under the conditions of submerged and not-submerged sand at water temperatures of 25±0.6℃. Following intrasinus and oral administration, the plasma concentration-time data for florfenicol were best described as a two-compartment open model with non and first-order absorption respectively, the pharmacokinetic equation:CiS=10.274e-2.295t+6.96e-0.109t,Cis =9.525e-2.793t+7.33e-0.108t and Cpo=4.281e-1.011t+8.038e-0.098t-12.319 e-18.793t, Cpo =0.042e-0.378t+8.294e-0.091t-8.336 e-10.684t, respectively. After intrasinus administration to Penaeus japonicus under the conditions of submerged and not-submerged sand,and the main pharmacokinetic parameters were as follows: tmax=0.083h,0.083h;Cmax=15.26,14.82μg/mL;t1/2α=0.302h,0.348h;t1/2β=6.347h,6.412h. It indicated more quickly absorption, higher peak plasma concentration, and faster elimination by intrasinus administration than by oral administration. The difference of pharmacokinetic characteristic of Penaeus japonicus under the two kinds of conditions is not significant. The half-period of absorption, distribution and elimination of Penaeus japonicus under the condition of submerged sand is slightly faster than that of not-submerged sand. The metabolism of florfenicol in the hemolymph, muscle and liver of Penaeus japonicus showed faster absorption.The elimination of the muscle is faster than hemolymph and liver. Florfenicol was established to shrimp bacterial disease, at the intervals of 13.6 hours, with the dose of 25.27mg/kg and 27.55 mg/kg under the submerged and not-submerged sand, respectively.