甲磺酸培氟沙星在山羊体内的药动学及在鸡体内的药效学研究
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摘要
本试验研究了甲磺酸培氟沙星(Pefloxacine Mesylate,PM)在山羊体内的药动学特征,及其体外抗菌活性和对试验性感染大肠杆菌鸡的疗效。
1山羊单剂量快速静注甲磺酸培氟沙星10 mg/kg,8 h内不同时间14次颈静脉采血,高效液相色谱法测定血药浓度。结果表明,甲磺酸培氟沙星在山羊体内的药物动力学配置符合无吸收因素二室开放模型。其药-时曲线最佳方程为:C = 9.3680e ?5 .6806 t + 9.4885e?0.4393t;主要药物动力学参数:分布半衰期t1/2α= 0.1678 h±0.1298 h,消除相半衰期t1/2β=1.6322 h±0.3189 h,药-时曲线下面积AUC=24.7542μg·mL-1·h±6.4560μg·mL-1·h,表观分布容积Vd=0.9676 L·kg-1±0.1498 L·kg-1,体清除率CLB=0.4219 L·kg-1·h-1±0.0832 L·kg-1·h-1。结果显示,甲磺酸培氟沙星在山羊体内分布迅速而广泛,消除较快。
2采用试管二倍稀释法,以盐酸环丙沙星和氟哌酸为对照,研究了甲磺酸培氟沙星对金黄色葡萄球菌、无乳链球菌、大肠杆菌、沙门氏菌和铜绿假单胞菌的体外抗菌活性,测定了MIC和MBC。结果表明,甲磺酸培氟沙星对5种细菌的MIC分别为:1、2、0.25、0.5和8μg/mL,MBC分别为:1、4、1、0.5和8μg/mL;盐酸环丙沙星对5种细菌的MIC分别为:0.5、0.03、0.03、0.03和1μg/mL,MBC分别为:1、0.12、0.12、0.06和4μg/mL;氟哌酸对5种细菌的MIC分别为:2、2、1、1和8μg/mL,MBC分别为2、4、1、1、32μg/mL。结果显示,甲磺酸培氟沙星对革兰氏阴性菌有良好的抗菌作用,对革兰氏阳性菌亦有抗菌活性,对铜绿假单胞菌有抗菌活性,但作用较弱。甲磺酸培氟沙星的抗菌活性弱于盐酸环丙沙星,强于氟哌酸。
3鸡只人工感染大肠杆菌后,应用甲磺酸培氟沙星25 mg/L、50 mg/L、100 mg/L和盐酸环丙沙星50 mg/L混饮进行治疗。经统计分析表明,100 mg/L甲磺酸培氟沙星组和50 mg/L盐酸环丙沙星组的治愈率显著高于甲磺酸培氟沙星中、低剂量组(P<0.05)。100 mg/L甲磺酸培氟沙星及50 mg/L盐酸环丙沙星对鸡的增重显著高于感染对照组(P<0.01);25 mg/L甲磺酸培氟沙星和50 mg/L甲磺酸培氟沙星对鸡的增重与感染对照组差异不显著(P>0.05);甲磺酸培氟沙星中、低剂量组与甲磺酸培氟沙星高剂量组和盐酸环丙沙星组之间存在显著或极显著差异(P<0.05或0.01);甲磺酸培氟沙星高剂量组与盐酸环丙沙星组之间差异不显著(P>0.05)。由此可看出,甲磺酸培氟沙星中、低剂量组治疗效果不理想,高剂量组与盐酸环丙沙星组的治疗效果较明显,且100 mg/L甲磺酸培氟沙星组与50 mg/L盐酸环丙沙星组治疗效果相当。
The study was divided into three parts. The first studied the pharmacokinetics of Pefloxacine Mesylate (PM) in goats; the second studied the antibacterial activity in vitro of PM; the third studied the pharmacodynamics of PM against artificially infected Escherichia coli in chickens.
1 Goats were treated with a single dosage of PM (10 mg/kg) intravenously and rapidly, while the blood samples were collected from jugular vein within 8 hour post giving drug. The concentrations of PM in serum were determined by high performance liquid chromatography (HPLC). The results showed that the two-compartment open model with first-order disabsorption factor adequately describes concentrations of PM in serum disposition and the best concentration-time equations are: C = 9.3680e ?5 .6806 t + 9.4885e?0.4393t. The primary pharmacokinetic parameters of PM are: t1/2α=0.1678 h±0.1298 h, t1/2β=1.6322 h±0.3189 h, AUC=24.7542μg·mL-1·h±6.4560μg·mL-1·h, Vd=0.9676 L·kg-1±0.1498 L·kg-1, CLB=0.4219 L·kg-1·h-1±0.0832 L·kg-1·h-1. It will be seen that the distribution of PM in vivo is rapid and abroad, and the elimination of PM in vivo is rapid.
2 Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of PM, Ciprofloxacin·HCl and Norfloxacin against Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli, Salmonella and Pseudomonas aeruginosa were detemined by two-fold diltution method in vitro.The MICs of PM were 1, 2, 0.25, 0.5, 8μg/mL, respectively. The MBCs of PM were 1, 4, 1, 0.5, 8μg/mL, respectively. The MICs of Ciprofloxacin·HCl were 0.5, 0.03, 0.03, 0.03, 1μg/mL. The MBCs of Ciprofloxacin·HCl were 1, 0.12, 0.12, 0.06, 4μg/mL. The MICs of Norfloxacin were 2, 2, 1, 1, 8μg/mL. The MBCs of Norfloxacin were 2, 4, 1, 1, 32μg/mL. The results showed that the antimicrobial action of PM against Gram-negative bacteria (G-) was very good and against Gram-positive bacteria (G+) was also good, but against Pseudomonas aeruginosa was weak. The antimicrobial action of PM was weaker than Ciprofloxacin·HCl, but better than Norfloxacin.
3 At first, the chickens were infected by Escherichia coli artificially. All the therapeutic groups of chickens were medicated for 3 days via drinking water with PM (25 mg/L, 50 mg/L, 100 mg/L) and Ciprofloxacin·HCl (50 mg/L). It will be seen that the cure rates of the high- dosage group of PM and Ciprofloxacin·HCl group were higher than that of middle-dosage group and low-dosage group of PM (P<0.05). The effect of weigh gain to chickens of the high-dosage group of PM was equivalent to that of Ciprofloxacin·HCl group (P>0.05), and obviously higher than that of infective control group (P<0.01). The effect of weigh gain to chickens of middle-dosage group and low-dosage group of PM were obviously lower than that of high-dosage group of PM and Ciprofloxacin·HCl group (P<0.05或0.01). The results showed that the curative effect of the middle-dosage group and low-dosage group of PM were not ideal, but the curative effect of the high-dosage group of PM and Ciprofloxacin·HCl group were good.
1山羊单剂量快速静注甲磺酸培氟沙星10 mg/kg,8 h内不同时间14次颈静脉采血,高效液相色谱法测定血药浓度。结果表明,甲磺酸培氟沙星在山羊体内的药物动力学配置符合无吸收因素二室开放模型。其药-时曲线最佳方程为:C = 9.3680e ?5 .6806 t + 9.4885e?0.4393t;主要药物动力学参数:分布半衰期t1/2α= 0.1678 h±0.1298 h,消除相半衰期t1/2β=1.6322 h±0.3189 h,药-时曲线下面积AUC=24.7542μg·mL-1·h±6.4560μg·mL-1·h,表观分布容积Vd=0.9676 L·kg-1±0.1498 L·kg-1,体清除率CLB=0.4219 L·kg-1·h-1±0.0832 L·kg-1·h-1。结果显示,甲磺酸培氟沙星在山羊体内分布迅速而广泛,消除较快。
2采用试管二倍稀释法,以盐酸环丙沙星和氟哌酸为对照,研究了甲磺酸培氟沙星对金黄色葡萄球菌、无乳链球菌、大肠杆菌、沙门氏菌和铜绿假单胞菌的体外抗菌活性,测定了MIC和MBC。结果表明,甲磺酸培氟沙星对5种细菌的MIC分别为:1、2、0.25、0.5和8μg/mL,MBC分别为:1、4、1、0.5和8μg/mL;盐酸环丙沙星对5种细菌的MIC分别为:0.5、0.03、0.03、0.03和1μg/mL,MBC分别为:1、0.12、0.12、0.06和4μg/mL;氟哌酸对5种细菌的MIC分别为:2、2、1、1和8μg/mL,MBC分别为2、4、1、1、32μg/mL。结果显示,甲磺酸培氟沙星对革兰氏阴性菌有良好的抗菌作用,对革兰氏阳性菌亦有抗菌活性,对铜绿假单胞菌有抗菌活性,但作用较弱。甲磺酸培氟沙星的抗菌活性弱于盐酸环丙沙星,强于氟哌酸。
3鸡只人工感染大肠杆菌后,应用甲磺酸培氟沙星25 mg/L、50 mg/L、100 mg/L和盐酸环丙沙星50 mg/L混饮进行治疗。经统计分析表明,100 mg/L甲磺酸培氟沙星组和50 mg/L盐酸环丙沙星组的治愈率显著高于甲磺酸培氟沙星中、低剂量组(P<0.05)。100 mg/L甲磺酸培氟沙星及50 mg/L盐酸环丙沙星对鸡的增重显著高于感染对照组(P<0.01);25 mg/L甲磺酸培氟沙星和50 mg/L甲磺酸培氟沙星对鸡的增重与感染对照组差异不显著(P>0.05);甲磺酸培氟沙星中、低剂量组与甲磺酸培氟沙星高剂量组和盐酸环丙沙星组之间存在显著或极显著差异(P<0.05或0.01);甲磺酸培氟沙星高剂量组与盐酸环丙沙星组之间差异不显著(P>0.05)。由此可看出,甲磺酸培氟沙星中、低剂量组治疗效果不理想,高剂量组与盐酸环丙沙星组的治疗效果较明显,且100 mg/L甲磺酸培氟沙星组与50 mg/L盐酸环丙沙星组治疗效果相当。
The study was divided into three parts. The first studied the pharmacokinetics of Pefloxacine Mesylate (PM) in goats; the second studied the antibacterial activity in vitro of PM; the third studied the pharmacodynamics of PM against artificially infected Escherichia coli in chickens.
1 Goats were treated with a single dosage of PM (10 mg/kg) intravenously and rapidly, while the blood samples were collected from jugular vein within 8 hour post giving drug. The concentrations of PM in serum were determined by high performance liquid chromatography (HPLC). The results showed that the two-compartment open model with first-order disabsorption factor adequately describes concentrations of PM in serum disposition and the best concentration-time equations are: C = 9.3680e ?5 .6806 t + 9.4885e?0.4393t. The primary pharmacokinetic parameters of PM are: t1/2α=0.1678 h±0.1298 h, t1/2β=1.6322 h±0.3189 h, AUC=24.7542μg·mL-1·h±6.4560μg·mL-1·h, Vd=0.9676 L·kg-1±0.1498 L·kg-1, CLB=0.4219 L·kg-1·h-1±0.0832 L·kg-1·h-1. It will be seen that the distribution of PM in vivo is rapid and abroad, and the elimination of PM in vivo is rapid.
2 Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of PM, Ciprofloxacin·HCl and Norfloxacin against Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli, Salmonella and Pseudomonas aeruginosa were detemined by two-fold diltution method in vitro.The MICs of PM were 1, 2, 0.25, 0.5, 8μg/mL, respectively. The MBCs of PM were 1, 4, 1, 0.5, 8μg/mL, respectively. The MICs of Ciprofloxacin·HCl were 0.5, 0.03, 0.03, 0.03, 1μg/mL. The MBCs of Ciprofloxacin·HCl were 1, 0.12, 0.12, 0.06, 4μg/mL. The MICs of Norfloxacin were 2, 2, 1, 1, 8μg/mL. The MBCs of Norfloxacin were 2, 4, 1, 1, 32μg/mL. The results showed that the antimicrobial action of PM against Gram-negative bacteria (G-) was very good and against Gram-positive bacteria (G+) was also good, but against Pseudomonas aeruginosa was weak. The antimicrobial action of PM was weaker than Ciprofloxacin·HCl, but better than Norfloxacin.
3 At first, the chickens were infected by Escherichia coli artificially. All the therapeutic groups of chickens were medicated for 3 days via drinking water with PM (25 mg/L, 50 mg/L, 100 mg/L) and Ciprofloxacin·HCl (50 mg/L). It will be seen that the cure rates of the high- dosage group of PM and Ciprofloxacin·HCl group were higher than that of middle-dosage group and low-dosage group of PM (P<0.05). The effect of weigh gain to chickens of the high-dosage group of PM was equivalent to that of Ciprofloxacin·HCl group (P>0.05), and obviously higher than that of infective control group (P<0.01). The effect of weigh gain to chickens of middle-dosage group and low-dosage group of PM were obviously lower than that of high-dosage group of PM and Ciprofloxacin·HCl group (P<0.05或0.01). The results showed that the curative effect of the middle-dosage group and low-dosage group of PM were not ideal, but the curative effect of the high-dosage group of PM and Ciprofloxacin·HCl group were good.
引文
[1] 杨宝峰主编. 药理学(第 6 版)[M]. 北京:人民卫生出版社,2004.
[2] Appelbaum P C, Hunter P A. The fluoroquinolone antibacterial: past, present, and future perspectives[J]. Int J Antimicrob Agents, 2000, 16(1): 5-15.
[3] Mather R, Karenchak L M, Romanowski E G. Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics[J]. Am J Ophthalmol, 2002, 133(4): 463-466.
[4] 王浴生,周黎明,洪诤. 氟喹诺酮类药物不良反应的机制与化学结构的关系[J]. 药物不良反应杂志,2005,6:401-407.
[5] 洪昌容,金永宽,蒋在赫. 有 7-(4-氨基甲基-肟)吡咯烷取代基的新喹啉羧酸衍生物和其制法[P]. CN: 1114959A(CA, 1996, 124: 289515h; EP, 688772).
[6] Pendland S L, Neuhauser M M, Garey K W. Comparative killing rates of gatifloxacin and ciprofloxacin against 14 clinical isolates: impact of bacerial strain and antibiotic concentration[J]. Diagn Microbiol Infect Dis, 2002, 44(1): 59-61.
[7] 李文平,李志万. 喹诺酮类药物的发展现状[J]. 中国兽药杂志,2002,36(9):37-39.
[8] Tojima M, Chiba K, Yoshida H. Perparation of oxoquinolonecarboxylic acids, their esters and salts antimicrobial agents[P]. JP: 1160578, 1999-04-02.
[9] 李江波,邹建卫,林瑞森等. 5 位取代基对喹诺酮构效关系的影响因素[J]. 科技通报,2000,16(3):198-199.
[10] Dougherty T J, Beaulier D, Barrett J F. Novel qunolones and the impact on resistance[J]. Drug Discovery Today, 2001, 6 (2): 52-67.
[11] Ore S W, Cooper C S, Schultz C C, etc. Quinolone and naphthyridinecarboxylic acid antibacterials[P]. WO: 0132655, 2001-11-03.
[12] Emura M, Takahashi H, Miyauchi R, etc. Preparation of 7-[3-(cycloalkyla minomethylpyrrolidin) -1-yl]quinolone derivatives as antibacterial agents[P]. WO: 0031062, 2000-11-24.
[13] Yun S, Jung Y, Lee J, etc. Antimicrobial quinolone derivatives and process for the preparation thereof[P]. KP: 9703501, 1997-05-18.
[14] Alovero F L, Pan X, Morris J E, etc. Engineering the specificity of fluoroquinolones: Benzenesulfonamide modification at C-7 of ciprofloxacin change its target in Streptococcus pneumoniae[J]. Antimicorb Agents Chemother, 2000, 44(13): 320-335.
[15] Shibata T, Fukui H, Natio T, etc. Preparation of optically active quinolinecarboxylic acid derivatives and salts there of as antibacterial agentsp[P]. WO: 9633992, 1996-10-31.
[16] 李江波,曹维良,林瑞森,等. 1-环丙基-6-氟-7-取代喹诺酮抗 HIV 活性的定量构效关系[J]. 化学学报,2001,59(6):832-834.
[17] Domagala J M. Structure-activity and structure-side-effect relationships for the quinolone antibacterials[J]. Journal of Antimicrobial Chemotherapy, 1994, 33(5): 685-706.
[18] Stein G E. The 4-quinolone antibiotics: past, present, and future[J]. Pharmacotherapy, 1988, 8(2): 301-304.
[19] Tillotson G S. Quinolones:structure-activity relationships and future predictions[J]. Journal of Med Microbiol, 1996, 44(2): 320-324.
[20] Just P M. Overview of the fluoroquinolone antibiotics[J]. Pharmacotherapy, 1993, 13(suppl 2): 5-17.
[21] Rosential N V, Adam D. Quinolone antibacterials: An update of their pharmacology and therapeutic use[J]. Drugs, 1994, 47(6): 872-901.
[22] Ping W, Laura E L, Kenneth L D, etc. Mechanism of action of the Des-F(6) quinolone BMS-284756 measured by supercoiling inhibition and cleavable complex assays[J]. Antimicorb Agents Chemother, 2001, 45(14): 3660-3676.
[23] Aminimanizani A, Beringer P, Jelliffe R. Comparative pharmacokinetics and pharmacodynamics of the newer fluoroquinolone antibacterials[J]. Clin Pharmacokinet, 2001, 17(4): 331-341.
[24] 范柏. 喹诺酮类抗菌药的作用机制及细菌耐药性的研究进展[J].国外医药抗生素分册,2004,25(1):27-29.
[25] Pruul H, Mcdouald P J. Lomefloxacin-induced modification of the kinetics of growth of Gram-negative bacteria and susceptibility to phagocytic killing by human neutrophils[J]. Antimicrob Chemother, 1990, 25: 91-103.
[26] Okuda J, Hayakawa E, Nishibuchi M, etc. Sequence analysis of the gyrA and parC homologues of a wild-type strain of Vibro parahaemolyticus and its fluoroquinolone-resistant mutants[J]. Antimicrob Agents Chemother, 1999, 43(5): 1156.
[27] 马红霞,邓旭明,欧阳红生. 细菌多重耐药分子机制的研究进展[J]. 国外医药抗生素分册,2002,23(3):102-105.
[28] Ghosh A S, Ahamed J, Chauhan K K, etc. Involvement of an efflux system in high-level fluoroquinolone resistance of Shigella dysenteriae[J]. Biochem Biophys Res Commun, 1998, 242(1): 54-56.
[29] Markham P N. Inhibition of the emergence of ciprofloxacin resis tance in streptococas prumoniae by the maltidrug efflux inhibitor reserpine[J]. Antimicorb Agents Chemother, 1999, 43: 988-993.
[30] 潘晓娴,唐英春. 喹诺酮类抗菌药耐药机制研究进展[J]. 中国抗感染化疗杂志,2005,5(3):187-191.
[31] Mignot A, Guillaume M, Brault M, etc. Multiple-dose pharmacokinetics and excretion balance of gatifloxacin, a new fluoroquinolone antibiotic,following oral administration to healthy Caucasian volunteers[J]. Chemotherapy, 2002, 48(3): 116-121.
[32] 张菁,郁继诚,施耀国,等. 左氧氟沙星药代动力学/药效学研究[J]. 中华医学杂志,2005,85(27):1926-1932.
[33] Zhanel G, Ennis K, Vercaigne L, etc. A critical review of the fluoroquinolone[J]. Drugs, 2002, 62(2): 13-19.
[34] Robson R A. Quinolone pharmacokinetics[J]. Int J Antimicrob Agents, 1992, 2(1): 3-10.
[35] 陈杖榴,肖田安. 人工合成抗菌药——氟喹诺酮类[J]. 中国家禽,2002,24(11):35-37.
[36] Wintvrouw M, Daelemans D, Pamnecouque C, etc. Broad spectrum antiviral acitivity and mechanism of antiviral action of the fluoroquinolone derivative K-12[J]. Antivir Chem Chemother, 2000, 9(5): 403-409.
[37] Amir A, Paul B, Roger J. Comparative Phamacokinetics and Phamacodynamics of the newer fluoroquinolone antibacterials[J]. Clin Pharmacokinet, 2001, 40(3): 169-181.
[38] 肖田安,陈杖榴. 氟喹诺酮类药物在动物体内的药动学研究进展[J]. 中国兽药杂志,2000,22(1):57-59.
[39] Schentag J J. Pharmacokinetics and pharmacodynamic predictors of antimicrobial efficacy: moxifloxacin and Stretococcus penumonae[J]. J Chemother, 2002, 14(suppl 2): 13-21.
[40] 张京. 新喹诺酮类药物在社区获得性呼吸道感染中的应用价值[J]. 中华结合和呼吸杂志,2001,12(4):45-48.
[41] Zhanel G G, Noreddin A M. Pharmacokinetics and pharmacodynamic of the new fluoroquinolones: focus on respiratory infections[J]. Curr Opin Phqrmacol, 2001, 11(5): 459-463.
[42] Jones R N, Andes D R, Mandell L A. Gatifloxacin used for therapy of outpatient community-acquired pneumonia caused by Streptococcus pneumonia[J]. Digan Microbial Infect Dis, 2002, 44(1): 93-100.
[43] 仲兆金. 喹诺酮类药物在老年人中的使用[J]. 国外医药抗生素分册,2001,22(3):126-127.
[44] Hurst M, Lamb H, Scott L, etc. Levofloxacin:an updated review of its use in the treatment of bacterial infections[J]. Drugs, 2002, 62(14): 2127-2167.
[45] 邱银生,吴 佳. 动物专用氟喹诺酮类药物研究进展[J]. 中国兽药杂志,1998,32(3):46-48.
[46] 徐士新. 我国对抗菌药物耐药性应采取的措施[J]. 中国兽药杂志,2001,35(6):39-41.
[47] Halliwel R F, Davery P G, Lambert J J. Antagonisal of GABA receptor by 4-quinolones[J]. J Antimicorb Chemother, 1993, 31: 457-461.
[48] Domagala J M. Structure-activaintdy structure-side-effectrelaionships for quinolone antibactrieals[J]. J Antimicorb Chemother, 1994, 23: 685-688.
[49] Schmuck G, Scharmann A, Schlater G, etc. Determination of the excitatory potencyes of different fluoroquinolones in the centrol nervous system by an invitro model[J]. J Antimicorb Chemother, 1998, 42: 1831-1839.
[50] Sahlmann R. Clinical toxicological aspects of fluroquinolones[J]. Toxicol Leff, 2002, 127: 269-273.
[51] 李引乾,扈文杰. 培氟沙星在兽医临床中的应用[J]. 动物医学进展,1997,18(4):8-11.
[52] Robinstein E, Camm J. Cordiotoxicity of fluoroquinolones[J]. J Antimicorb Chemother, 2002, 49: 593- 597.
[53] Hagiwara T, Satch S, Kasai Y, etc. A comparative study of the fluoroquinolones antibacterial gents on the actionpotential duration in guineapig ventil ciarmyocardia[J]. Jpn Phamacol, 2001, 87: 231-235.
[54] 汪复,张婴元 主编. 实用抗感染治疗学[M]. 北京,人民卫生出版社,2004.
[55] Ball P, Mandell L, Niki Y, etc. Comparativetol erabitity of the newer fluoroquinolone antibacterials[J]. Drug Saf, 1999, 21: 407-412.
[56] Child S. Safety of fluoroquinolones antibiot: Ficocus on molecularstracture[J]. Infect Urol, 2000, 13: 3-6.
[57] 刘展心,李丽莹,胡宝荣. 喹诺酮类抗菌药物的合理应用及不良反应[J]. 中国药事,2005,19(6):380-382.
[58] 曲芬. 喹诺酮类药物的软骨毒性[J]. 国外医药抗生素分册,1998,19:61-67.
[59] 蒋锦,刘明亮. 氟喹诺酮类药物的安全性[J]. 国外医药抗生素分册,2003,24:226-232.
[60] Schuter G. Ciprofloxacin review of potential toxicity[J]. Am J Med, 1987, 82(14): 91-97.
[61] 刘晓岩,孙学琴,侯杰. 环丙沙星对幼龄大鼠软骨的影响[J]. 中国抗生素杂志,2000,24:47-51.
[62] 曲芬,姜素梅,李瑞霞,等. 孕妇血浆、羊水及胎儿血浆、软骨中环丙沙星的测定[J]. 中国抗生素杂志,1998,23:151-156.
[63] 兰红,曲芬,姜素梅,等. 环丙沙星致胎儿关节软骨的免疫组织学研究[J]. 中国抗生素杂志,2001,26:298-303.
[64] 陈正贤. 喹诺酮类抗菌药物的不良反应[J]. 医师进修杂志,2005,28(11):9-12.
[65] 操继跃. 氟喹诺酮类药物药理学研究进展[J]. 中国兽药杂志,1993,27(3):44-49.
[66] Spersen F. Resistance to antibiotice used in dermatological practice[J]. Br J Dermatol, 1998, 139(suppl 1): 4-8.
[67] 国际医药服务公司 编. 世界新药[M]. 北京:中国医药科技出版社,1987.
[68] 李仲昆,粱月晴,林 杉. 培氟沙星药理作用及临床应用简介[J]. 医药导报,1999,18(2):110.
[69] 国家药典委员会 编. 中国药典(2005 年版,二部)[S]. 北京:化学工业出版社,2005.
[70] 张 莉,吴文蓉,张淑华,等. 国产甲磺酸培氟沙星体内抗菌活性试验[J]. 四川生理科学杂志,1998,20(3):25-28.
[71] 于守凡. 培氟沙星在目前抗菌疗法中的地位[J]. 国外医药抗生素分册,2002,23(4):179-187.
[72] King A, Philips I. The comparative in vitro activity of pefloxacin[J]. Antimicrob Chemother, 1986, 17(Suppl B): 1.
[73] Auckenthaler R, Michea-Hamzehaur M, Pechere J C. In vitro activity of newer quinolones against aerobic bacteria[J]. Antimicrob Chemother, 1986, 17(Suppl B): 29.
[74] 江明性 主编. 药理学(第 3 版)[M]. 北京:人民卫生出版社,1993.
[75] 徐榕青,邓思珊,夏志林,等. 甲磺酸培氟沙星人体药代动力学研究[J]. 中国临床药理学与治疗学杂志,1996,1(2):94-96.
[76] 邵志高,张静,张宏文,等. 培氟沙星口服给药的药物动力学研究[J]. 中国医院药学杂志,1995,15(1):7-10.
[77] 肖永红,王其南,钱元恕,等. 依诺沙星、环丙沙星、氧氟沙星和培氟沙星在健康志愿者体内的药代动力学研究[J]. 重庆医科大学学报,1994,19(3):177-179.
[78] Frydman A M, Roux Y L, Lefebvre M A, etc. Pharmacokinetics of pefloxacin after repeated intravenous and oral administration (400mg bid) in young healthy volunteers[J]. Antimicrob Chemother, 1986, 17(suppl B): 56-65.
[79] 李华,陆红,张朴,等. 甲磺酸培氟沙星多次给药的药代动力学与合理给药方案研究[J]. 中国药学杂志,1996,31(1):37-40.
[80] 邱银生,朱式欧,江美安,等. 甲磺酸培氟沙星在犬体内的药物动力学及片剂的生物利用度[J]. 中国医药工业杂志,1994,25(12):546-548.
[81] 吴兆亮. 培氟沙星的临床应用[J]. 安徽医药,1999,3(4):19-20.
[82] 傅得兴. 甲磺酸培氟沙星的药理及临床评价[J]. 首都医药,2000,7(11):21-22.
[83] 于丽璇,车胜荣 主编. 精选新药手册[M]. 西安:陕西科学技术出版社,1995.
[84] 邢界红,张兆喜. 新药甲磺酸培氟沙星的药理及临床疗效[J]. 哲里木畜牧学院学报,2000,10(1):41-44.
[85] 高仲阳,张 弋,徐彦贵. 培氟沙星的药理及临床应用[J]. 天津药学,1998,10(2):26-28.
[86] 商晓华,伍湘瑾. 甲磺酸培氟沙星注射液的抗菌作用研究[J]. 辽宁药物与临床,1999,2(4):11-12.
[87] 薛光运,郭云霞,田方利. 甲磺酸培氟沙星治疗泌尿系统感染的临床疗效[J]. 中华现代内科学杂志,2004,1(4):375.
[88] 金哲虎,金贤玉,王 鹏,等.培氟沙星治疗急性淋病 32 例[J].延边大学医学学报,1998,21(5):189-190.
[89] 罗开国,张 辉. 培氟沙星的临床应用[J]. 中国医院药学杂志,2002,22(4):233-234.
[90] 李 为,李立津,刘德孟,等. 培氟沙星治疗 821 例细菌感染临床评价[J]. 中国抗生素杂志,1995,20(2):144-147.
[91] 贾辅忠,朱剑秋,黄士元,等. 培氟沙星治疗伤寒的临床研究[J]. 中华传染病杂志,1994,12(6):134-136.
[92] 候星燕,张平生,黄士元. 培氟沙星治疗伤寒 35 例疗效分析[J]. 苏州医学院学报,1995,15(5):928-929.
[93] 李引乾,刘清玉,李富娥,等. 长效沙星注射液的安全性试验及临床疗效观察[J]. 西北农业大学学报,1997,25(4):51-54.
[94] 戴自英. 实用抗菌药物学(第 2 版)[M]. 上海:上海科学技术出版社,1998.
[95] 曾锦旗,孙正军,陈万成. 培氟沙星研究与临床应用[J]. 中华外科杂志,2001,39(6):486-487.
[96] 马利军,吴纪珍,孙长义,等. 培氟沙星对老年肺炎患者肾功能影响[J]. 河南医学研究,2003,12(1):37-40.
[97] Scaglion F, Scamazo F, Areidiacono M, etc. Comparative activities pefloxacin and ciprofloxacin in the treatment of chronic respiratory tract infections[J]. J Chemother, 1995, 7(1): 140-145.
[98] 陈术辉. 喹诺酮类抗菌药的联合用药与不良反应[J]. 湖南医学,2000,17(6):369-371.
[99] 连儒强,张立蘅,吴照刚. 喹诺酮类药物不良反应及药物相互作用[J]. 中国医院药学杂志,2002,22(2):108-110.
[100] 周 曦. 甲磺酸培氟沙星致变态反应 1 例[J]. 成都医药,2002,28(6):365.
[101] 张 洁,王 倩. 52 例培氟沙星的不良反应分析[J]. 中国医院药学杂志,2005,25(8):791-792.
[102] 刘 芳,张春红,张 犇. 培氟沙星与其它药物在临床上的合理用药[J]. 张家口医学院学报,1999,16(5):42.
[103] 彭天吉,文爱东,李淑均. 培氟沙星和氧氟沙星对氨茶碱药动学的影响[J]. 药学进展,1999,23(2):109-112.
[104] 张致平. 喹诺酮类抗菌药物的研究进展[J]. 中国抗生素杂志,1992,17(2):87-97.
[105] 操继跃,卢从笑. 兽医药物动力学[M]. 北京:中国农业出版社,2005.
[106] 李俊锁,邱月明,王超. 兽药残留分析[M]. 上海:上海科学技术出版社,2002.
[107] [美]M·吉伯尔迪,D·佩里尔 著,朱家壁 译. 药物动力学[M]. 北京:科学出版社,1981.
[108] 曾衍霖. 药物动力学中的第二个计算问题——原始数据的权量与线数字模型房室的确定[J]. 药学学报,1980,15(9):574.
[109] 蒋新国,朱芳海,奚念朱,等. HPLC 测定甲磺酸培氟沙星血药浓度及其应用于人体生物利用度研究[J]. 中国药学杂志,1994,29(7):410-413.
[110] 杜黎明,卫洪清,张俊燕,等. 反相高效液相色谱法同时测定 6 种氟喹诺酮类药物[J]. 色谱,2003,21(5):503-506.
[111] Montay G. Absorption, distribution, metabolic fate, and elimination of pefloxacin in mice, rats, dogs, monkeys and humans. Antimicrob Agents Chemother, 1984, 25: 463.
[112] 孙红祥,严新星. 长效恩诺沙星注射液体外释药实验及在山羊体内的药动学研究[J]. 畜牧兽医学报,2004,35(1):111-114.
[113] 李健强,李六金 主编. 兽医微生物学实验实习指导[M]. 西安:陕西科学技术出版社,1999.
[114] 徐叔云,卞如濂,陈 修 主编. 药理实验方法学(第 3 版)[M]. 北京:人民卫生出版社,2003.
[2] Appelbaum P C, Hunter P A. The fluoroquinolone antibacterial: past, present, and future perspectives[J]. Int J Antimicrob Agents, 2000, 16(1): 5-15.
[3] Mather R, Karenchak L M, Romanowski E G. Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics[J]. Am J Ophthalmol, 2002, 133(4): 463-466.
[4] 王浴生,周黎明,洪诤. 氟喹诺酮类药物不良反应的机制与化学结构的关系[J]. 药物不良反应杂志,2005,6:401-407.
[5] 洪昌容,金永宽,蒋在赫. 有 7-(4-氨基甲基-肟)吡咯烷取代基的新喹啉羧酸衍生物和其制法[P]. CN: 1114959A(CA, 1996, 124: 289515h; EP, 688772).
[6] Pendland S L, Neuhauser M M, Garey K W. Comparative killing rates of gatifloxacin and ciprofloxacin against 14 clinical isolates: impact of bacerial strain and antibiotic concentration[J]. Diagn Microbiol Infect Dis, 2002, 44(1): 59-61.
[7] 李文平,李志万. 喹诺酮类药物的发展现状[J]. 中国兽药杂志,2002,36(9):37-39.
[8] Tojima M, Chiba K, Yoshida H. Perparation of oxoquinolonecarboxylic acids, their esters and salts antimicrobial agents[P]. JP: 1160578, 1999-04-02.
[9] 李江波,邹建卫,林瑞森等. 5 位取代基对喹诺酮构效关系的影响因素[J]. 科技通报,2000,16(3):198-199.
[10] Dougherty T J, Beaulier D, Barrett J F. Novel qunolones and the impact on resistance[J]. Drug Discovery Today, 2001, 6 (2): 52-67.
[11] Ore S W, Cooper C S, Schultz C C, etc. Quinolone and naphthyridinecarboxylic acid antibacterials[P]. WO: 0132655, 2001-11-03.
[12] Emura M, Takahashi H, Miyauchi R, etc. Preparation of 7-[3-(cycloalkyla minomethylpyrrolidin) -1-yl]quinolone derivatives as antibacterial agents[P]. WO: 0031062, 2000-11-24.
[13] Yun S, Jung Y, Lee J, etc. Antimicrobial quinolone derivatives and process for the preparation thereof[P]. KP: 9703501, 1997-05-18.
[14] Alovero F L, Pan X, Morris J E, etc. Engineering the specificity of fluoroquinolones: Benzenesulfonamide modification at C-7 of ciprofloxacin change its target in Streptococcus pneumoniae[J]. Antimicorb Agents Chemother, 2000, 44(13): 320-335.
[15] Shibata T, Fukui H, Natio T, etc. Preparation of optically active quinolinecarboxylic acid derivatives and salts there of as antibacterial agentsp[P]. WO: 9633992, 1996-10-31.
[16] 李江波,曹维良,林瑞森,等. 1-环丙基-6-氟-7-取代喹诺酮抗 HIV 活性的定量构效关系[J]. 化学学报,2001,59(6):832-834.
[17] Domagala J M. Structure-activity and structure-side-effect relationships for the quinolone antibacterials[J]. Journal of Antimicrobial Chemotherapy, 1994, 33(5): 685-706.
[18] Stein G E. The 4-quinolone antibiotics: past, present, and future[J]. Pharmacotherapy, 1988, 8(2): 301-304.
[19] Tillotson G S. Quinolones:structure-activity relationships and future predictions[J]. Journal of Med Microbiol, 1996, 44(2): 320-324.
[20] Just P M. Overview of the fluoroquinolone antibiotics[J]. Pharmacotherapy, 1993, 13(suppl 2): 5-17.
[21] Rosential N V, Adam D. Quinolone antibacterials: An update of their pharmacology and therapeutic use[J]. Drugs, 1994, 47(6): 872-901.
[22] Ping W, Laura E L, Kenneth L D, etc. Mechanism of action of the Des-F(6) quinolone BMS-284756 measured by supercoiling inhibition and cleavable complex assays[J]. Antimicorb Agents Chemother, 2001, 45(14): 3660-3676.
[23] Aminimanizani A, Beringer P, Jelliffe R. Comparative pharmacokinetics and pharmacodynamics of the newer fluoroquinolone antibacterials[J]. Clin Pharmacokinet, 2001, 17(4): 331-341.
[24] 范柏. 喹诺酮类抗菌药的作用机制及细菌耐药性的研究进展[J].国外医药抗生素分册,2004,25(1):27-29.
[25] Pruul H, Mcdouald P J. Lomefloxacin-induced modification of the kinetics of growth of Gram-negative bacteria and susceptibility to phagocytic killing by human neutrophils[J]. Antimicrob Chemother, 1990, 25: 91-103.
[26] Okuda J, Hayakawa E, Nishibuchi M, etc. Sequence analysis of the gyrA and parC homologues of a wild-type strain of Vibro parahaemolyticus and its fluoroquinolone-resistant mutants[J]. Antimicrob Agents Chemother, 1999, 43(5): 1156.
[27] 马红霞,邓旭明,欧阳红生. 细菌多重耐药分子机制的研究进展[J]. 国外医药抗生素分册,2002,23(3):102-105.
[28] Ghosh A S, Ahamed J, Chauhan K K, etc. Involvement of an efflux system in high-level fluoroquinolone resistance of Shigella dysenteriae[J]. Biochem Biophys Res Commun, 1998, 242(1): 54-56.
[29] Markham P N. Inhibition of the emergence of ciprofloxacin resis tance in streptococas prumoniae by the maltidrug efflux inhibitor reserpine[J]. Antimicorb Agents Chemother, 1999, 43: 988-993.
[30] 潘晓娴,唐英春. 喹诺酮类抗菌药耐药机制研究进展[J]. 中国抗感染化疗杂志,2005,5(3):187-191.
[31] Mignot A, Guillaume M, Brault M, etc. Multiple-dose pharmacokinetics and excretion balance of gatifloxacin, a new fluoroquinolone antibiotic,following oral administration to healthy Caucasian volunteers[J]. Chemotherapy, 2002, 48(3): 116-121.
[32] 张菁,郁继诚,施耀国,等. 左氧氟沙星药代动力学/药效学研究[J]. 中华医学杂志,2005,85(27):1926-1932.
[33] Zhanel G, Ennis K, Vercaigne L, etc. A critical review of the fluoroquinolone[J]. Drugs, 2002, 62(2): 13-19.
[34] Robson R A. Quinolone pharmacokinetics[J]. Int J Antimicrob Agents, 1992, 2(1): 3-10.
[35] 陈杖榴,肖田安. 人工合成抗菌药——氟喹诺酮类[J]. 中国家禽,2002,24(11):35-37.
[36] Wintvrouw M, Daelemans D, Pamnecouque C, etc. Broad spectrum antiviral acitivity and mechanism of antiviral action of the fluoroquinolone derivative K-12[J]. Antivir Chem Chemother, 2000, 9(5): 403-409.
[37] Amir A, Paul B, Roger J. Comparative Phamacokinetics and Phamacodynamics of the newer fluoroquinolone antibacterials[J]. Clin Pharmacokinet, 2001, 40(3): 169-181.
[38] 肖田安,陈杖榴. 氟喹诺酮类药物在动物体内的药动学研究进展[J]. 中国兽药杂志,2000,22(1):57-59.
[39] Schentag J J. Pharmacokinetics and pharmacodynamic predictors of antimicrobial efficacy: moxifloxacin and Stretococcus penumonae[J]. J Chemother, 2002, 14(suppl 2): 13-21.
[40] 张京. 新喹诺酮类药物在社区获得性呼吸道感染中的应用价值[J]. 中华结合和呼吸杂志,2001,12(4):45-48.
[41] Zhanel G G, Noreddin A M. Pharmacokinetics and pharmacodynamic of the new fluoroquinolones: focus on respiratory infections[J]. Curr Opin Phqrmacol, 2001, 11(5): 459-463.
[42] Jones R N, Andes D R, Mandell L A. Gatifloxacin used for therapy of outpatient community-acquired pneumonia caused by Streptococcus pneumonia[J]. Digan Microbial Infect Dis, 2002, 44(1): 93-100.
[43] 仲兆金. 喹诺酮类药物在老年人中的使用[J]. 国外医药抗生素分册,2001,22(3):126-127.
[44] Hurst M, Lamb H, Scott L, etc. Levofloxacin:an updated review of its use in the treatment of bacterial infections[J]. Drugs, 2002, 62(14): 2127-2167.
[45] 邱银生,吴 佳. 动物专用氟喹诺酮类药物研究进展[J]. 中国兽药杂志,1998,32(3):46-48.
[46] 徐士新. 我国对抗菌药物耐药性应采取的措施[J]. 中国兽药杂志,2001,35(6):39-41.
[47] Halliwel R F, Davery P G, Lambert J J. Antagonisal of GABA receptor by 4-quinolones[J]. J Antimicorb Chemother, 1993, 31: 457-461.
[48] Domagala J M. Structure-activaintdy structure-side-effectrelaionships for quinolone antibactrieals[J]. J Antimicorb Chemother, 1994, 23: 685-688.
[49] Schmuck G, Scharmann A, Schlater G, etc. Determination of the excitatory potencyes of different fluoroquinolones in the centrol nervous system by an invitro model[J]. J Antimicorb Chemother, 1998, 42: 1831-1839.
[50] Sahlmann R. Clinical toxicological aspects of fluroquinolones[J]. Toxicol Leff, 2002, 127: 269-273.
[51] 李引乾,扈文杰. 培氟沙星在兽医临床中的应用[J]. 动物医学进展,1997,18(4):8-11.
[52] Robinstein E, Camm J. Cordiotoxicity of fluoroquinolones[J]. J Antimicorb Chemother, 2002, 49: 593- 597.
[53] Hagiwara T, Satch S, Kasai Y, etc. A comparative study of the fluoroquinolones antibacterial gents on the actionpotential duration in guineapig ventil ciarmyocardia[J]. Jpn Phamacol, 2001, 87: 231-235.
[54] 汪复,张婴元 主编. 实用抗感染治疗学[M]. 北京,人民卫生出版社,2004.
[55] Ball P, Mandell L, Niki Y, etc. Comparativetol erabitity of the newer fluoroquinolone antibacterials[J]. Drug Saf, 1999, 21: 407-412.
[56] Child S. Safety of fluoroquinolones antibiot: Ficocus on molecularstracture[J]. Infect Urol, 2000, 13: 3-6.
[57] 刘展心,李丽莹,胡宝荣. 喹诺酮类抗菌药物的合理应用及不良反应[J]. 中国药事,2005,19(6):380-382.
[58] 曲芬. 喹诺酮类药物的软骨毒性[J]. 国外医药抗生素分册,1998,19:61-67.
[59] 蒋锦,刘明亮. 氟喹诺酮类药物的安全性[J]. 国外医药抗生素分册,2003,24:226-232.
[60] Schuter G. Ciprofloxacin review of potential toxicity[J]. Am J Med, 1987, 82(14): 91-97.
[61] 刘晓岩,孙学琴,侯杰. 环丙沙星对幼龄大鼠软骨的影响[J]. 中国抗生素杂志,2000,24:47-51.
[62] 曲芬,姜素梅,李瑞霞,等. 孕妇血浆、羊水及胎儿血浆、软骨中环丙沙星的测定[J]. 中国抗生素杂志,1998,23:151-156.
[63] 兰红,曲芬,姜素梅,等. 环丙沙星致胎儿关节软骨的免疫组织学研究[J]. 中国抗生素杂志,2001,26:298-303.
[64] 陈正贤. 喹诺酮类抗菌药物的不良反应[J]. 医师进修杂志,2005,28(11):9-12.
[65] 操继跃. 氟喹诺酮类药物药理学研究进展[J]. 中国兽药杂志,1993,27(3):44-49.
[66] Spersen F. Resistance to antibiotice used in dermatological practice[J]. Br J Dermatol, 1998, 139(suppl 1): 4-8.
[67] 国际医药服务公司 编. 世界新药[M]. 北京:中国医药科技出版社,1987.
[68] 李仲昆,粱月晴,林 杉. 培氟沙星药理作用及临床应用简介[J]. 医药导报,1999,18(2):110.
[69] 国家药典委员会 编. 中国药典(2005 年版,二部)[S]. 北京:化学工业出版社,2005.
[70] 张 莉,吴文蓉,张淑华,等. 国产甲磺酸培氟沙星体内抗菌活性试验[J]. 四川生理科学杂志,1998,20(3):25-28.
[71] 于守凡. 培氟沙星在目前抗菌疗法中的地位[J]. 国外医药抗生素分册,2002,23(4):179-187.
[72] King A, Philips I. The comparative in vitro activity of pefloxacin[J]. Antimicrob Chemother, 1986, 17(Suppl B): 1.
[73] Auckenthaler R, Michea-Hamzehaur M, Pechere J C. In vitro activity of newer quinolones against aerobic bacteria[J]. Antimicrob Chemother, 1986, 17(Suppl B): 29.
[74] 江明性 主编. 药理学(第 3 版)[M]. 北京:人民卫生出版社,1993.
[75] 徐榕青,邓思珊,夏志林,等. 甲磺酸培氟沙星人体药代动力学研究[J]. 中国临床药理学与治疗学杂志,1996,1(2):94-96.
[76] 邵志高,张静,张宏文,等. 培氟沙星口服给药的药物动力学研究[J]. 中国医院药学杂志,1995,15(1):7-10.
[77] 肖永红,王其南,钱元恕,等. 依诺沙星、环丙沙星、氧氟沙星和培氟沙星在健康志愿者体内的药代动力学研究[J]. 重庆医科大学学报,1994,19(3):177-179.
[78] Frydman A M, Roux Y L, Lefebvre M A, etc. Pharmacokinetics of pefloxacin after repeated intravenous and oral administration (400mg bid) in young healthy volunteers[J]. Antimicrob Chemother, 1986, 17(suppl B): 56-65.
[79] 李华,陆红,张朴,等. 甲磺酸培氟沙星多次给药的药代动力学与合理给药方案研究[J]. 中国药学杂志,1996,31(1):37-40.
[80] 邱银生,朱式欧,江美安,等. 甲磺酸培氟沙星在犬体内的药物动力学及片剂的生物利用度[J]. 中国医药工业杂志,1994,25(12):546-548.
[81] 吴兆亮. 培氟沙星的临床应用[J]. 安徽医药,1999,3(4):19-20.
[82] 傅得兴. 甲磺酸培氟沙星的药理及临床评价[J]. 首都医药,2000,7(11):21-22.
[83] 于丽璇,车胜荣 主编. 精选新药手册[M]. 西安:陕西科学技术出版社,1995.
[84] 邢界红,张兆喜. 新药甲磺酸培氟沙星的药理及临床疗效[J]. 哲里木畜牧学院学报,2000,10(1):41-44.
[85] 高仲阳,张 弋,徐彦贵. 培氟沙星的药理及临床应用[J]. 天津药学,1998,10(2):26-28.
[86] 商晓华,伍湘瑾. 甲磺酸培氟沙星注射液的抗菌作用研究[J]. 辽宁药物与临床,1999,2(4):11-12.
[87] 薛光运,郭云霞,田方利. 甲磺酸培氟沙星治疗泌尿系统感染的临床疗效[J]. 中华现代内科学杂志,2004,1(4):375.
[88] 金哲虎,金贤玉,王 鹏,等.培氟沙星治疗急性淋病 32 例[J].延边大学医学学报,1998,21(5):189-190.
[89] 罗开国,张 辉. 培氟沙星的临床应用[J]. 中国医院药学杂志,2002,22(4):233-234.
[90] 李 为,李立津,刘德孟,等. 培氟沙星治疗 821 例细菌感染临床评价[J]. 中国抗生素杂志,1995,20(2):144-147.
[91] 贾辅忠,朱剑秋,黄士元,等. 培氟沙星治疗伤寒的临床研究[J]. 中华传染病杂志,1994,12(6):134-136.
[92] 候星燕,张平生,黄士元. 培氟沙星治疗伤寒 35 例疗效分析[J]. 苏州医学院学报,1995,15(5):928-929.
[93] 李引乾,刘清玉,李富娥,等. 长效沙星注射液的安全性试验及临床疗效观察[J]. 西北农业大学学报,1997,25(4):51-54.
[94] 戴自英. 实用抗菌药物学(第 2 版)[M]. 上海:上海科学技术出版社,1998.
[95] 曾锦旗,孙正军,陈万成. 培氟沙星研究与临床应用[J]. 中华外科杂志,2001,39(6):486-487.
[96] 马利军,吴纪珍,孙长义,等. 培氟沙星对老年肺炎患者肾功能影响[J]. 河南医学研究,2003,12(1):37-40.
[97] Scaglion F, Scamazo F, Areidiacono M, etc. Comparative activities pefloxacin and ciprofloxacin in the treatment of chronic respiratory tract infections[J]. J Chemother, 1995, 7(1): 140-145.
[98] 陈术辉. 喹诺酮类抗菌药的联合用药与不良反应[J]. 湖南医学,2000,17(6):369-371.
[99] 连儒强,张立蘅,吴照刚. 喹诺酮类药物不良反应及药物相互作用[J]. 中国医院药学杂志,2002,22(2):108-110.
[100] 周 曦. 甲磺酸培氟沙星致变态反应 1 例[J]. 成都医药,2002,28(6):365.
[101] 张 洁,王 倩. 52 例培氟沙星的不良反应分析[J]. 中国医院药学杂志,2005,25(8):791-792.
[102] 刘 芳,张春红,张 犇. 培氟沙星与其它药物在临床上的合理用药[J]. 张家口医学院学报,1999,16(5):42.
[103] 彭天吉,文爱东,李淑均. 培氟沙星和氧氟沙星对氨茶碱药动学的影响[J]. 药学进展,1999,23(2):109-112.
[104] 张致平. 喹诺酮类抗菌药物的研究进展[J]. 中国抗生素杂志,1992,17(2):87-97.
[105] 操继跃,卢从笑. 兽医药物动力学[M]. 北京:中国农业出版社,2005.
[106] 李俊锁,邱月明,王超. 兽药残留分析[M]. 上海:上海科学技术出版社,2002.
[107] [美]M·吉伯尔迪,D·佩里尔 著,朱家壁 译. 药物动力学[M]. 北京:科学出版社,1981.
[108] 曾衍霖. 药物动力学中的第二个计算问题——原始数据的权量与线数字模型房室的确定[J]. 药学学报,1980,15(9):574.
[109] 蒋新国,朱芳海,奚念朱,等. HPLC 测定甲磺酸培氟沙星血药浓度及其应用于人体生物利用度研究[J]. 中国药学杂志,1994,29(7):410-413.
[110] 杜黎明,卫洪清,张俊燕,等. 反相高效液相色谱法同时测定 6 种氟喹诺酮类药物[J]. 色谱,2003,21(5):503-506.
[111] Montay G. Absorption, distribution, metabolic fate, and elimination of pefloxacin in mice, rats, dogs, monkeys and humans. Antimicrob Agents Chemother, 1984, 25: 463.
[112] 孙红祥,严新星. 长效恩诺沙星注射液体外释药实验及在山羊体内的药动学研究[J]. 畜牧兽医学报,2004,35(1):111-114.
[113] 李健强,李六金 主编. 兽医微生物学实验实习指导[M]. 西安:陕西科学技术出版社,1999.
[114] 徐叔云,卞如濂,陈 修 主编. 药理实验方法学(第 3 版)[M]. 北京:人民卫生出版社,2003.