Microsoft Word 赵青松_new_.doc

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1 45 3 Vol.45, No OCEANOLOGIA ET LIMNOLOGIA SINICA May, 2014 (Portunus trituberculatus) * ( ) (Portunus trituberculatus),, 25mg/kg,, 3P97 :, ;,, ;,,,,,,, 10d ; (Portunus trituberculatus); ; ; S948 doi: /hyhz (florfenicol),,, (Samuelsen et al, 1998; Stefan et al, 2004;, 2005;, 2010;, 2011;, 2012), (Oncorhynchus mykiss) (Pseudosciaena crocea) (Gadus morhua) (Salmo salar) (Acipenser baeri) (Anguilla anguilla) (Silurus asotus) (Crucian carp) (Fenneropenaeus chinensis) (Procambarus clarkii) (Penaeus vannamei Boone)(Pelodiscus sinensis) (, 2004; Park et al, 2006;, 2010;, 2011;, 2012), (Portunus trituberculatus),,,, (, 2002;, 2006),,,, (, 2010),, *, Y ;, 2010R ;, 2011B ;, 2011C50008 ;, XKL11093,, zhaoqingsong@ nbu.edu.cn : , :

2 3 : (P. trituberculatus), (90±25)g, 220,,, 25±1, (21±2) C, ph 8.0±0.5, 15d,, 50%, 1.2 ( 8g/L, 20g/L, EDTA 3.36g/L, μL/L); ( 10%, ); ( 99.2%, ) 1.3 Agilent Technologies1200 ( Agilent ), G1311A G1314B G1311A Chemstation G1329A ; R206D 1.4 (Vibrio alginolyticus) (2010) 1.5 (, 2011) 25mg/kg, h 1.. 1, 4 C 10min(3000r/min), ;, 20 C 5, 1.6, 0.5mL 0.5g, 4mL, 5min, 4 C 10min(6000r/min), 20mL,, 45 C, 1mL, 2min, 0.45μm, 20 C, (HPLC), 1.7 : Diaimonsil TM C18 (150mm 16mm i.d., 5μm); :.. = 27:73(v/v), 0.45μm ; : 1.0mL/min; : 223nm; : 30 C; ph 7.0; : 20μL μg/mL, 20 C μg/mL HPLC,,, S/N=2 (LOD) μg/mL(μg/g), 1.6, 3 (%)= / 100%3 31d3, 3d, 1.10 Microsoft Excel 2003 ; 3P μg/mL (X)(Y), Y 32.51X+0.79, R 2 1 S/N=2, 0.025μg/mL 2.2 (84.8±1.6)% (88.0±8.9)% (94.2±2.0)%, 80%; , , 5%,, ,,

3 570 45, 12h, 3.23μg/g, 1.64μg/g,, 2h, Fig.1 1 Change of florfenicol concentration with time in hepatopancreas of P. trituberculatus 2h 4h, 24h,, 168h 240h 0.1μg/mL, 98.6% 2.4 Fig.2 Fig.3 2 Change of florfenicol concentration with time in muscle of P. trituberculatus 3 Change of florfenicol concentration with time in plasma of P. trituberculatus 3P97, 1 2, (T 1/2β ) (CLs) (V d ), (T 1/2Ka ) (T peak ) (C max ) CLs V d, Ka T 1/2Ka 0.25h,,, 6.85μg/g 3.32μg/g;, 2h 15.16% 33.21%; T 1/2β T peak V d (P<0.05); Ka T 1/2Ka T peak C max AUC, Ka T 1/2β AUC, AUC CLs (P<0.01) Tab.1 表 1 氟苯尼考在健康和患病三疣梭子蟹组织内的药动学方程 Equations of florfenicol concentration with time in healthy and diseased P. trituberculatus R 2 R 2 C=9.22e 3.07t +1.48e 0.02t 10.70e 15.89t 0.97 C=19.28e 3.29t +1.42e 0.01t 20.71e 4.36t 0.88 C=6.75e 0.67t +1.44e 0.01t 8.19e 2.42t 0.97 C=19.01e 0.68t +1.44e 0.01t 20.45e 0.87t 0.97 C=15.23e 0.25t +0.69e 0.02t 15.92e 0.70t 0.99 C=18.07e 0.25t +1.71e 0.01t 19.78e 0.39t 0.99

4 3 : 571 表 2 氟苯尼考在健康和患病三疣梭子蟹体内的药动学参数 Tab.2 Pharmacokinetic parameters of florfenicol in healthy and diseased P. trituberculatus A(μg/mL) a b d e B(μg/mL) α(/h) β(/h) Ka(/h) a b c d e f K 10 (/h) K 12 (/h) K 21 (/h) T 1/2Ka (h) a b c d e f T 1/2α (h) T 1/2β (h) a b c d e f T peak (h) a b c d e f C max (μg/ml) a b c d e f AUC(μg/(mL h)) a b c d e f CLs(L/(kg h)) a b c d e f V d (L/kg) b c d e f A: ; B: ; α: ; β: ; Ka: ; K 10 : ; K 12 : ; K 21 : ; T 1/2Ka : ; T 1/2α : ; T 1/2β : ; T peak : ; C max : ; AUC: ; CLs: ; V d : (P<0.05) 3,, ; 0.25h,,, (, 2001;, 2002;, 2012) (Park et al, 2006;, 2010;, 2011;, 2012;, 2012), (2011)(2006) (2007),,,,,, (, 2011;, 2006),, (Baggot, 1980) Uno(1996) ; (2006)(2011),, ;, (, 2003)(, 2001;, 2003)(, 1996),,,,,, (2006) (2003),,,,

5 572 45,,,,, V d,,, (, 2003) 0.1mg/kg, 1 3, 168h 240h, 0.1mg/kg,, 10d,,, , 25(4): ,,, , 24(4): ,,, , 21(40): ,,, , 33(2): ,,, , 30(4): ,,, , 36(9): ,, :, 95 97,,, , 28(Supp1.): 63 68,,, , (2): ,,, , 3(5): ,,, , 30(2): , :,,, ( ), 23(4): 35 40, , (3): 24 25,,, ( ), 16(2): 92 96,,, ( ), 20(1): 23 26,,, , 33(4): ,,, , 12(4): ,,, , 15(4): ,,, , 34(1): ,,, , (5): 42 43,,, EGCG (Pelteobagrus vachelli)., 43(5): ,,, , 21(1): 86 89,, , 30(6): Baggot J D, Distribution of antimicrobial agents in normal and diseased animals. Journal of the American Veterinary Medical Association (USA), 176(10): Park B K, Lim J H, Kim M S et al, Pharmacokinetics of florfenicol and its metabolite, florfenicol amine, in the Korean catfish (Silurus asotus). Journal of Veterinary Pharmacology and Therapeutics, 29(1): Samuelsen O B, Hjeltnes B, Glette J, Efficacy of orally administered florfenicol in the treatment of furunculosis in Atlantic salmon. Journal Aquat Anim Health, 10(1): Stefan S, Corinna K, Axel C et al, Molecular basis of bacterial resistance to chloramphenicol and florfenicol. FEMS Microbiology Reviews, 28(5): Uno K, Pharmacokinetic study of oxytetracycline in healthy and vibriosis-infected ayu (Plecoglossus altivelis). Aquaculture, 143(1): 33 42

6 3 : 573 PHARMACOKINETICS OF FLORFENICOL IN DISEASE MODEL OF PORTUNUS TRITUBERCULATUS ZHAO Qing-Song, JIN Shan, CHEN Yin-Er, QIN Fang-Jin, WANG Xi-Bo, WANG Guo-Liang (School of Marine sciences of Ningbo University, Ningbo , China) Abstract To understand the metabolic differences of florfenicol in healthy and diseased Portunus trituberculatus, the pharmacokinetics of florfenicol were investigated based on Vibrio alginolyticus disease model. P. trituberculatus was orally administered in a single dose of 25mg/kg in water temperature (21±2) C. Tissues of haemolymph, muscle, and hepatopancreas were sampled and measured using high performance liquid chromatography (HPLC). Results show that florfenicol in healthy P. trituberculatus have a similar concentration-time curve with that of diseased animals. The profiles of the three tissues could be described by a two-compartment open model with a time lag. Florfenicol can be distributed unevenly in all tissues, absorbed most quickly in hepatopancreas and most slowly in plasma. Compared with the healthy P. trituberculatus, the rate of absorption and elimination in diseased P. trituberculatus slowed, the peak time delayed and half-liveextended, clean-up ratio and maximum drug concentration decreased, apparent volume of distribution and the area under the curve increased. These pharmacokinetic parameters showed that florfenicol in diseased P. trituberculatus changed greatly in absorption, distribution, elimination, and metabolism. According to the maximum residue limit (MRL) of 0.1mg/kg in tissues, the withdrawal period should not be less than 10 days under experiment condition. Key words florfenicol; Portunus trituberculatus; disease model; Vibrio alginolyticus; pharmacokinetics

Microsoft Word 曹伏君_new_.doc

Microsoft Word 曹伏君_new_.doc 45 2 Vol.45, No.2 2014 3 OCEANOLOGIA ET LIMNOLOGIA SINICA Mar., 2014 (Lethrinus erythropterus) * ( 524025) Wright (Lethrinus erythropterus),,,, ; ; ; Q954.56 doi: 10.11693/hyhz20140100011 (Lethrinus erythropterus)