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Studies On Pharmocokinetics And Tissue Elimination Of Chloramphenicol And Norfloxacin In Bastard Halibut

Posted on:2004-02-14Degree:MasterType:Thesis
Country:ChinaCandidate:X H LiuFull Text:PDF
GTID:2133360092996736Subject:Aquaculture
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The pharmacokinetics and tissue elimination of CAP in paralichthys olivaceus are the first studied in this thesis. The clinical effect of CAP is impersonality evaluated from the view of pharmacokinetics and the disserve is adequately recognized, which is adaptive to the nowaday demands.The concentrations of CAP are determined by High Performance Liquid Chromatography, and the pharmacokinetic data derived from the experiment are analyzed by non-compartmental methods based on statistical moment theory. The results indicate that: (1)The concentration-time curves of CAP shows an obvious double-peak phenomenon after oral administration at a dose of 80mg.kg-1. The main pharmacokinetic parameters are as follows: Tmax(1) is about 2h, Cmax(1) is 15.01,11.80,10.35,8.56,5.21 g'ml-1 in gill, liver, kidney, blood, muscle respectively; Cmax(2) is smaller than the corresponding Cmax(1), Tmax(2) is 8h; AUC is 176.87, 133.77, 118.77, 65.33, 50.36mg'h'L"1 in kidney, gill, liver, blood, muscle respectively; t1/2 4.89~10.39h; MRT 8.67~17.05h. The results show that the CAP can be absorbed quickly after oral administration in paralichthys olivaceus, but the residence time is long; According to MRLs, the time of maitaining effective drug levels in tissues is about 8~16h, However, drug concentration in muscle is only effective to partial pathogens during almost all the time. It is considered that CAP is not the most effective drug in preventing and curing the bacterial infection of paralichthys olivaceus. (2) After oral administration at dose of 40mg kg-1 for five consecutive days,The elimination characteristics of CAP in five tissues can be described by the equations as follows: Ckidney=5.4153e-0.006t, Cgill=1.2526e-0.0091t, Cliver=2.8286e-0.0113t, Cblood=0.3341e-0.0114t, Cmuscle=0.8262e-0.0176t; T1/2 are 39.38h(Tmuscle), 60.79h(Tblood), 61.33h(Tliver), 77.01(Tgill)h, 115.50h(Tkidney) respectively. It shows that the elimination of CAP from the body is retarded and the residual amount in the body is great; especially, residual levels in the kidney and liver are highest, which are severe harmful to human body.Quinolones are widely used in aquaculture and the studies lay particular stress on pharmacokinetics about clinical application currently, and that the study of regularity of depletion is neglected. Owing to above causes, the residues and depletion of norfloxacin are the first studied in paralichthys olivaceus in this thesis. Blood, muscle, liver, kidney and gill are sampled after oral administration at dose of 30mg kg-1 for five consecutive days. The samples are homogenated with pH7.4 sodium phosphate buffer and extracted with acetonitrile after shaking, and the tissue concentrations of Norfloxacin aredeterminated using reversed-phase HPLC(RP-HPLC). The elimination equations of NFLX in five tissues are as follows: Ckidney=0.2382e-0.)028t, Cgil,=0.1284e-0.0052t, Cblood=0.2784e-0.0054t, CMver=0.1554e-0.0147t, Cmuslee=0.5345e-0.0375t; The overall recovery is 71.37%~82.13%; The limit of detection is 0.005ug . ml-1; T1/2 are Tkidney247.5h, Tgill133.27h, Tblood128.33h, Tlver47.14h, Tmusciel8.48h respectively. The results show that the elimination speed is deeply defferent in five tissues; Kidney and gill are main reservoirs of norfloxain in paralichthys olivaceus; It is suggested that the drug withdrawl period is10~15d in the light of the maximum residue limits of 50 g . kg-1.
Keywords/Search Tags:Chloramphenicol, Norfloxacin, Bastard halibut (paralichthys olivaceus), Pharmacokinetics, Elimination regularity
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