Microsoft Word - 李晖_news_.doc

Size: px

Start display at page:

Download "Microsoft Word - 李晖_news_.doc"

句友却
7 years ago
Views:

1 肌注和口服药饵麻保沙星在日本对虾体内的药代动力学比较李晖 1, 李健 2, 孙铭 2 2, 梁俊平 (1., ; 2., ) 摘要 : 在水温 (25±0.6) 条件下, 分别以和 30 mg/kg 剂量给健康日本对虾血窦注射肌注和口服药饵麻保沙星后, 用高效液相色谱法测定药物浓度, 采用 DAS2.0 药动学软件对血药浓度进行分析, 主要比较了肌注和口服药饵两种给药方式下麻保沙星在日本对虾体内的药代动力学差异结果显示, 血窦注射给药后, 麻保沙星在日本对虾体内药物动力学最佳模型为无级吸收二室开放模型, 表达方程为 : C 血窦注射 = e t +8.28e t ; 肌注和口服药饵麻保沙星后, 在日本对虾体内的代谢过程均符合一级吸收二室开放模型, 表达方程为 C 肌肉注射 = e 1.153t +7.90e 0.059t e 11.73t, C 口服药饵 = e 0.33t +3.01e 0.051t e 0.408t 与口服药饵给药后药代动力学参数比较, 肌注给药后的 t max (0.25 h) t 1/2Ka (0.059 h) t 1/2α (0.601 h) 和 t 1/2β ( h) 均小于口服药饵给药的 t max (0.5 h) t 1/2Ka (1.697 h) t 1/2α (2.103 h) 和 t 1/2β ( h), 且 C max ( mg/l) 和 F(99.56%) 均大于口服药饵给药 C max ( mg/l) F(69.68%) 结果表明, 肌注麻保沙星在日本对虾体内的吸收分布和消除均快于口服药饵给药, 且比口服给药吸收较完全本实验将药动学参数与抗菌后效应 (PAE) 和最小抑菌浓度 (MIC) 相结合来探讨麻保沙星的给药方案, 建议在治疗日本对虾细菌性疾病时, 肌注 mg/kg, 每隔 13.6 h 一次 ; 口服 mg/kg, 每隔 11.8 h 一次关键词 : 日本对虾 ; 麻保沙星 ; 药代动力学 ; 给药方案中图分类号 : S948 文献标识码 : A 文章编号 : (2013) (Marsupenaeus japonicus) 20 80, 20,,,,,,,,, (marbofloxacin),, 1995 Vetoquinol [1],,, (Carassius auratus) [2-7] ; (Fenneropenaeus chinensis) [8-10],,,,,, : ; : : 863 (2012AA10A409); (CARS-47); ()( ) : (1982-),,,,, lihui319@163.com;,, Lijian@ysfri.ac.cn Marine Sciences / Vol. 37, No. 3 /

2 ,, (PAE) (MIC), 1 材料与方法 1.1 试验材料 1.1.1, 7.89 cm, 5.66 g,, 2, 1,, (25±0.6), 1.1.2, 99.5%, ;, 98.5%,, , 85% Agilent1100 (HPLC), WindowsNT4.0 HP, KL512, XHF-1, Eppendorf 1.2 试验方法 , :, 10 mg/kg, ; :, 10 mg/kg, h :, 30 mg/kg, 20 g h 8, 80 :, 1%,,, 1 min, r/min 5 min, , 1 g, 0.3 g 0.5 ml, 2 ml r/min 20 s; 2 ml, 10 s, 2 h, r/min 10 min,, 40, 1 ml, 2 ml, 0.2 μm g,, 100 ml, 100 mg/l, mg/l HPLC,,, [11] : Agilent Tc-C18(250 mm 4.6 mm, 5 µm); : : (0.01 mol/l, ph=3.42)=20:80(v:v);, 295 nm; 30 ; 1.0 ml/min, 20 μl mg/l 0.5 g 0.5 ml,, 3,, 样品实测药物浓度回收率 = 100% 样品理论药物浓度 1 d 5 5 d, (C V%), DAS2.0, 1 1/C 1/CC 3, AIC R 2, MIC, 64 / 2013 / 37 / 3

3 [12] : D= C Vd K τ / F, D: ; C: ; V d : ; K: ; : ; F: 2 结果 2.1 线性范围与最低检测限 0.01~5.00 mg/l, : Y = X , R 2 = 回收率与精密度 80.25%~93.84%, 1 ; 2.35%~3.27%, 3.26%~4.53%, 2, 70%, 10%,, 表 1 麻保沙星在三种组织中的回收率 Tab. 1 Recovery rate of marbofloxacin in three tissues (%) (mg/l) ± ± ± ± ± ± ± ± ± ± ± ±3.66 表 2 麻保沙星在 3 种组织中的变异系数 Tab. 2 Variation coefficient of marbofloxacin in three tissues (%) 2.35± ± ± ± ± ± 麻保沙星在日本对虾体内的药代动学特征 DAS2.0 3,,, : C = Ae αt Be βt ;,, : C = Ae αt Be βt (A B)e Kat 3 : C = e 1.396t 8.28e t C = e 1.153t 7.90e 0.059t e 11.73t C = e 0.33 t 3.01e 0.051t e 0.408t 3,,, (t 1/2α ) h, (t 1/2β ) h;,, (t 1/2α ) h, (t 1/2β ) h;,, (t 1/2α ) h, (t 1/2β ) h 1.5 h,,, mg/kg, (F) : F(%)=(AUC / /AUC ) (Dose Dose /) 100,, 100%;,, 99.56%;,, 69.68% ,, ,, ; 2, 0.25 h, h ;, h,,, 0.25 h (PAE) (MIC) [13] PAE, MIC PAE Marine Sciences / Vol. 37, No. 3 /

4 表 3 日本对虾血窦注射肌肉注射和口服药饵麻保沙星的药代动力学参数 Tab. 3 Pharmacokinetic parameters of marbofloxacin given by intravenous (10 mg/kg b.w.), intramuscular (10 mg/kg b.w.) or oral administration (30 mg/kg b.w.) to Marsupenaeus japonicus A mg/l B mg/l α 1/h β 1/h Ka 1/h t 1/2Ka h t 1/2α h t 1/2β h K 10 1/h K 12 1/h K 21 1/h AUC 0~t h mg/l t max h C max mg/l V d L/kg F % Fig. 1 Mean marbofloxacin concentration-time curve in plasma of Marsupenaeus japonicus after intramuscular and oral administration 3 MIC 1~4 mg/l, MIC PAE 0.49~1.25 h 10 mg/kg 12 h MIC, mg/kg 10 h MIC PAE,, PAE 1.6 h, PAE 1.8 h: 13.6 h, 2 - Fig. 2 Mean marbofloxacin concentration-time curve in tissues of Marsupenaeus japonicus after intramuscular administration 11.8 h D= C Vd K τ / F, mg/kg mg/kg, 16 mg/l 3 讨论 3.1 肌注和口服药饵麻保沙星在日本对虾体内的吸收特征 3, 66 / 2013 / 37 / 3

5 , F(99.56%), (69.68%) [9] F % 97.41%, ; [2, 8] F 87.94% 94.45%,,, 3.2 肌注和口服药饵麻保沙星在日本对虾体内的分布特征 3 - Fig. 3 Mean marbofloxacin concentration-time curve in tissues of Marsupenaeus japonicus after oral administration (10 mg/kg) 0.25 h, (0.95 h)(1.57 h)(0.91 h) [2,8-9], (0.147 h) [10] ; 2.0 h, (3.75 h) 15 h) [9,14], (1.35 h) [8], (1.94 h) (1.74 h) [6-7] [15],, [16] 1~2 min [17], 2 min, [18] t 1/2Ka h, (0.54 h) (0.27 h) [8,9], (0.028 h) [10] ; t 1/2Ka h, (1.16 h) (0.42 h) [8-9],,,,, P450 [19] ;,, ;,,, [20] t 1/2α (2.33 h)(2.87 h) [8-9], (0.893 h) [10] ; (2.31 h) (4.94 h) [8-9], (0.87 h) [7],, (0.27 h) (0.41 h) [21-22], (0.97 h) (1.66 h) [23-24] V d 10 mg/kg V d 0.90 L/kg, (0.16 L/kg) [14] (0.87 L/kg)(0.99 L/kg) [6-7], 3.3 肌注和口服药饵麻保沙星在日本对虾体内的消除特征 (5.47 h) (6.77 h)(6.27 h) (1.96 h) (4.33 h) [2,4,8,25-26], (17.38 h) [9], (9.866 h) [10] ; (7.15 h)(6.48 h) [6,8], (25.05 h)(22.98 h) [7,9], (13.33 h) [14],,,,, [27], [8] [9], Marine Sciences / Vol. 37, No. 3 /

6 [19,21,28-29],,, (6.494 h) (7.03 h) (1.69 h) (10.87 h) [21-24] ;, (7.903 h) (4.24 h) [17,30],, 3.4 药动参数与抗菌后效应 (PAE) 及最小抑菌浓度 (MIC) 结合给药方案探讨, (MIC), MIC,, 3~4 PAE MIC [31],,, PAE MIC MBC,,,, 4 小结 :,,,,,,,, mg/kg, 13.6 h; mg/kg, 11.8 h : [1],. [J]., 1998, 32 (3): [2] Carretero M, Rodriguez C, Sanandres M I, et al. Pharmacokinetics of marbofloxacin in mature horses after single intravenous and intramuscular administration [J]. Equine Veterinary Journal, 2002, 34 (4): [3] Schneider M, Valle M, Woehrle F. Pharmacokinetics of marbofloxacin in lactating cows after repeated intramuscular administrations and pharmacodynamics against mastitis isolated strains [J]. Journal of Dairy Science, 2004, 87(1): [4] Waxman S, Rodríguez C, González F, et al. Pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in adult goats [J]. Journal of Veterinary Pharmacology and Therapeutics, 2002, 24(6): [5] Boothe H W, Jones S A, Wilkie W S, et al. Evaluation of the concentration of marbofloxacin in alveolar macrophages and pul-monary epithelial lining fluid after administration in dogs [J]. American Journal of Veterinary Research, 2005, 66(10): [6] Albarellos G A, Montoya L, Landoni M F. Pharmacokinetics of marbofloxacin after single intravenous and repeat oral administration to cats [J]. The Veterinary Journal, 2005, 170: [7] Zhu Yanlei, Tan Yeping, Wang Chunmei, et al. Pharmacokinetics and tissue residues of marbofloxacin in crucian carp (Carassius auratus) after oral administration[j]. Aquaculture Research, 2009, 40: [8],,,. [J]., 2002, 22(3): [9],,,. (marbofloxacin)[j]., 2004, 24(2): [10],,,. [J]., 2008, 10(2): [11],, 喆,. [J]., 2010, 34(6): [12],,. ( 3 )[M]. :, [13],, 喆,. [J]., 2010, 17(1): [14] Marín O R P, Lai P, Laricchiuta G, et al. Pharmacokinetics of marbofloxacin after a single oral dose to loggerhead sea turtles (Caretta caretta) [J]. Research in Veterinary Science, 2009, 87: [15],,. [J]., 2003, 27(1): [16],,,. [J]., 2003, 27(1): [17],. [J]., 2006, 30(5): [18] Park E D, Lightner D V, Milner N, et al. Exploratory 68 / 2013 / 37 / 3

7 bioavailability and pharmacokinetic studies of sulphadimethoxine and ormetoprim in the penaeid shrimp, Penaeus vannamei [J]. Aquaculture, 1995, 130(2-3): [19].. :, 2005: [20],. [J]., 2007, 28(1): 1-3. [21],,,. [J]., 2004, 28(12): [22],,,. [J]., 2005, 22(8): 1-5. [23],,,. [J]., 2008, 31(2): [24],,. [J]., 2008, 27(2): [25] Jose Julio de Lucas, Casilda Rodrı guez, Samanta Waxman,Pharmacokinetics of marbofloxacin after intravenous and intramuscular administration to ostriches[j]. The Veterinary Journal, 2005, 170: [26],. [J]., 2001, 22(4): [27],,,. [J]., 2011, 32(2): [28] Bailey T A, Sheen R S, Silvanose C, et al. Pharmacokinetics of enrofloxacin after intravenous and oral administration in Houbara Bustard (Chlamydotis undulate macqueenii) [J]. J.VET. Pharmacol.Therap, 1998, 21: [29] Stoffregen D A, Wooster G A, Bustos P S, et al. Multiple route and dose pharmacokinetics of enrofloxacin in juvenile Atlantic Salmon [J]. J Vet Pharmacol Ther, 1997, 20(2): [30],. [J]., 1997, 21(4): [31],,. [J]., 2002, 7(2): 7-8. Pharmacokinetics of Marbofloxacin in kuruma prawn, Marsupenaeus japonicus following intramuscular and oral administration LI Hui 1, LI Jian 2, SUN Ming 2, LIANG Jun-Ping 2 (1.Shan Dong Vocational College Of Science&Technology, Weifang , China; 2.Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao , China) Received: Apr.,20,2012 Key words: Marsupenaeus japonicus; Marbofloxacin; Pharmacokinetics; Dosage regimen Abstract: The pharmacokinetics of intrasinusly, intramuscularly and orally administered marbofloxacin was determined in kuruma prawn, Marsupenaeus japonicus, with a single dose of 10 and 30 mg/kg body weight respectively, at water temperatures of 25 ±0.6. Following intramuscular and oral administration, the plasma concentra- tion-time data for enrofloxacin were best described as a two-compartment open model with first-order absorption and elimination with the pharmacokinetic equation: C im =15.521e 1.153t 7.90e 0.059t e 11.73t and C po = e 0.399t 3.01e 0.051t e 0.408t, respectively. After intramuscular and oral administration, the main pharmacokinetic parameters were as follows: t 1/2Ka and 1.697, t max 0.25 h and 2.0 h, t 1/2α h and h, C max mg/l and mg/l, F 99.56% and 69.68%, t 1/2β h and h, respectively. It indicated quicker absorption, wider distribution, higher peak plasma concentration, higher bioavailability and faster elimination by intramuscular administration than oral administration. In this study, pharmacokinetic parameters, post antibiotic effect (PAE) and the minimum inhibitory concentration (MIC) were combined to discuss the dosage regimen of marbofloxacin. The scheme of marbofloxacin was established to shrimp bacterial disease, at the intervals of 13.6 and 11.8 h, with the dose of and mg/kg by intramuscular and oral administration, respectively. ( 本文编辑 : 康亦兼 ) Marine Sciences / Vol. 37, No. 3 /

Microsoft Word 赵青松_new_.doc

Microsoft Word 赵青松_new_.doc 45 3 Vol.45, No.3 2014 5 OCEANOLOGIA ET LIMNOLOGIA SINICA May, 2014 (Portunus trituberculatus) * ( 315211) (Portunus trituberculatus),, 25mg/kg,, 3P97 :, ;,, ;,,,,,,, 10d ; (Portunus trituberculatus);