Comparative pharmacokinetics of marbofloxacin in healthy and Mannheimia haemolytica infected calves

The pharmacokinetics of marbofloxacin were investigated in healthy (n=8) and Mannheimia haemolytica naturally infected (n=8) Simmental ruminant calves following intravenous (i.v.) and intramuscular (i.m.) administration of 2 mg kg(-1) body weight. The concentration of marbofloxacin in plasma was measured using high performance liquid chromatography with ultraviolet detection. Following i.v. administration of the drug, the elimination half-life (t(1/2 beta)) and mean residence time (MRT) were significantly longer in diseased calves (8.2h; 11.13 h) than in healthy ones (4.6 h; 6.1 h), respectively. The value of total body clearance (CL(B)) was larger in healthy calves (3 ml min(-1) kg(-1)) than in diseased ones (1.3 ml min(-1) kg(-1)). After single intramuscular (i.m.) administration of the drug, the elimination half-life, mean residence time (MRT) and maximum plasma concentration (C(max)) were higher in diseased calves (8.0, 12 h, 2.32 microg ml(-1)) than in healthy ones (4.7, 7.4 h, 1.4 microg ml(-1)), respectively. The plasma concentrations and AUC following administration of the drug by both routes were significantly higher in diseased calves than in healthy ones. Protein binding of Marbofloxacin was not significantly different in healthy and diseased calves. The mean value for MIC of marbofloxacin for M. haemolytica was 0.1+/-0.06 microg ml(-1). The C(max)/MIC and AUC(24)/MIC ratios were significantly higher in diseased calves (13.0-64.4 and 125-618 h) than in healthy calves (8-38.33 and 66.34-328 h). The obtained results for surrogate markers of antimicrobial activity (C(max)/MIC, AUC/MIC and T > or = MIC) indicate the excellent pharmacodynamic characteristics of the drug in diseased calves with M. haemolytica, which can be expected to optimize the clinical efficacy and minimize the development of resistance.     

三穗鸭不同组织三种氟喹诺酮类药物残留分布研究

采用固相萃取-反相高效液相色谱法,对三穗鸭胸肉、腿肉、心脏、鸭胗和鸭肠等不同组织中氟喹诺酮含量进行检测。结果表明：各组织中环丙沙星与恩诺杀星含量均在国家标准限度内,沙拉沙星未检出。在不同组织中环丙沙星与沙拉沙星的残留规律类似。胸肉和腿肉中环丙沙星、恩诺沙星的含量显著高于其他组织,作为主要代谢器官的鸭胗和鸭肠中含量最少。     

高效液相色谱法测定鸡蛋中氟喹诺酮类药物残留量前处理方法的优化

建立了鸡蛋中环丙沙星、达氟沙星、恩诺沙星和沙拉沙星4种氟喹诺酮类药物残留测定的超高效液相色谱方法。样品经磷酸盐缓冲液提取后,用正己烷脱脂,C18固相萃取柱净化,反相高效液相色谱分离,荧光检测器测定。本方法的检测限为环丙沙星、恩诺沙星和沙拉沙星5 μg/kg,达氟沙星1 μg/kg。环丙沙星、恩诺沙星和沙拉沙星在2~200 ng/mL、达氟沙星在0.4～40 ng/mL范围内呈线性相关,相关系数r大于0.9999。在空白鸡蛋中添加环丙沙星、恩诺沙星和沙拉沙星5~50 μg/kg、达氟沙星1～10 μg/kg,4种氟喹诺酮类药物的平均回收率为82.2～101.3％,批内变异系数0.8～5.9％之间(n＝6),批间变异系数在1.0～6.6％之间(n＝4)。结果表明,该法灵敏、准确、特异性强,适用于鸡蛋中氟喹诺酮类药物残留的测定。     

Pharmacokinetics of enrofloxacin following intravenous administration to greater rheas: a preliminary study

The pharmacokinetic behaviour of enrofloxacin (ENR) and its active metabolite ciprofloxacin (CIP) were determined in six greater rheas following a single intravenous (i.v.) dose of 15 mg/kg bw. Plasma concentrations of ENR and CIP were simultaneously determined by a HPLC/u.v. method. Following i.v. administration, the plasma drug concentrations were best fitted by an open two-compartment model with a rapid distribution phase. The high volume of distribution (V(ss)=5.01 L/Kg) suggests good tissue penetration. ENR presents a high clearance (3.95 L/kg h) explaining the low AUC values (3.57 mg h/L) and a short permanence (t(1/2beta)=2.66 h and MRT=1.23 h). Ciprofloxacin comprised 14% of the total fluoroquinolone (ENR+CIP).     

氟喹诺酮类药物残留检测方法研究进展

已报道的氟喹诺酮类药物残留检测方法主要有微生物法、液相色谱法、高效液相色谱法、高效毛细管电泳法、液相色谱-质谱联用法、免疫测定法与免疫亲和色谱法等。就国内外有关FQs药物残留检测方法的研究进展进行了综述。     

猪源大肠埃希菌中质粒介导喹诺酮耐药（PMQR）基因的多样性研究

为研究陕西省关中猪源大肠埃希菌的耐药情况及质粒介导的喹诺酮耐药（PMQR）基因的流行性与多样性,于2017年4月-2018年11月从陕西关中地区数个养猪场分离获得470株大肠埃希菌,采用微量肉汤稀释法测定其对包括3 种氟喹诺酮类药物在内的6类抗菌药物的最小抑菌浓度（MIC）,PCR扩增检测其携带的PMQR基因,并分析PMQR基因阳性菌株gyrA和parC基因的质粒介导喹诺酮耐药决定区（QRDR）的突变情况。结果显示,陕西猪源大肠埃希菌对阿莫西林和土霉素的耐药率高达100%和98.51%,对阿米卡星、氟苯尼考、替米考星和头孢噻呋的耐药率分别为60.64%、52.98%、50.85%和44.47%,且  89.58%为多重耐药菌株。对3种氟喹诺酮类药物恩诺沙星、普多沙星和环丙沙星的耐药率分别为89.58%、  57.66%和56.80%。对美罗培南最为敏感,未发现耐药菌株,但有9株大肠埃希菌对美罗培南的敏感性为中介。对氟喹诺酮类药物耐药的菌株中,PMQR基因qnrS、 aac(6′)-Ib-cr、qnrB、qnrA、qnrD和 qepA的检出率分别为  36.52%、30.14%、17.38%、11.45%和2.49%,且55.30%的菌株携带1种PMQR基因,37.90%携带2种PMQR基因,6.40%携带3种PMQR基因,0.35%携带4种PMQR基因。在282株携带PMQR基因的菌株中,279株发生QRDR突变,其中以gyrA基因的Ser83Leu突变为主。132株PMQR基因阳性菌株parC基因发生Ser80Ile或Ser80Ile+Glu84Val突变。随着菌株所携带PMQR基因的增多,gyrA和parC基因的突变位点也相应增加,细菌的耐药水平也随之增加。     

兽用氟喹诺酮类在猪体内、外抗菌后效应初报

五种兽用氟喹诺酮药物在体外对猪链球菌、大肠杆菌均具有不同程度的抗菌后效应 (PAE) ,最长者可达3 2 3h ,且PAE受抗菌药物的种类及其浓度、细菌种类及接种量、药物与细菌的接触时间的影响。研究通过在猪的皮下埋植组织笼建立组织笼感染模型 ,成功的应用于沙拉沙星对猪链球菌、猪大肠杆菌的体内PAE研究。结果表明 ,3种浓度的沙拉沙星在体内对 2种细菌均获得了较体外长得多的PAE(P <0 0 1) ,其中对猪链球菌最长的体内PAE值达 3 84h ,对猪大肠杆菌最长的体内PAE值达 2 87h。     

耐氟喹诺酮类药物鸡源大肠杆菌gyrA基因QRDR的突变检测

用微量肉汤稀释法对180株鸡源大肠杆菌临床分离株进行了6种氟喹诺酮类药物的耐药性监测，大多数分离株对氟喹诺酮类药物表现出高耐药率（52．9％～93．30%）并呈多重耐药性。提取各菌株染色体DNA，对gyrA基因QRDR进行PCR扩增并测序。氨基序列分析结果显示：168株耐药菌株的第83位的氨基酸均发生了变异，由丝氨酸（S）变为亮氨酸（L）；对4种以上氟喹诺酮类药物有耐药性的107株分离株除第83位氨基酸发变异外，第87位氨基酸也发生了变异，88株由天冬氨酸（D）变为天冬酰氨（N），13株为酪氨酸（Y），5株变为甘氨酸（G），1株变为丙氨酸（A），由此表明鸡源大肠杆菌对氟喹诺类药物的耐药程度与gyrA基因QRDR的变异密切相关，第83位氨基酸变异是大肠杆菌现对氟喹诺酮类药物耐药的关键。     

Detection of enrofloxacin and its metabolite ciprofloxacin in equine hair

Hair analysis to detect drug administration has not been studied extensively in horses. This study aimed to (a) develop an analytical method for enrofloxacin and its metabolite ciprofloxacin in mane and tail hair, (b) relate measured values to doses, routes of administration, hair colour, and (c) demonstrate long-term detectability. Samples were extracted in trifluoroacetic acid at 70 degrees C. Extracts were cleaned-up by solid-phase extraction and analysed by high-performance liquid chromatography with UV-diode array detection. Analyte recoveries were > 87%. Horses were sampled after therapeutic enrofloxacin administration either orally at 7.5 mg/kg daily for 3-13 days or twice daily for 10-14 days (Group 1, n=7) or intravenously at 5.0 mg/kg daily for 12 and 15 days (Group 2, n=2). Enrofloxacin and ciprofloxacin were detected at concentrations up to 452 and 19 ng/mg, respectively, up to 10 months post-treatment. In vitro, enrofloxacin and ciprofloxacin were extensively bound to melanin (> 96%) and in vivo, their uptake was 40-fold greater in black than white hair. Enrofloxacin and ciprofloxacin concentrations correlated to enrofloxacin dose (r2=0.777 and r2=0.769). Enrofloxacin:ciprofloxacin ratios were 21:1 and 13:1 following intravenous and oral administration, respectively. Longitudinal analyte distributions correlated to treatment-sampling interval.     

水产品氟喹诺酮类药物残留检测研究进展

氟喹诺酮类药物是一类广谱高效抗茵药物,随着该药在水产养殖的普遍应用,其残留问题已引起广泛关注。在综述水产品中氟喹诺酮类药物残留检测方法的基础上,指出今后氟喹诺酮类药物残留检测将向着高灵敏度的联用技术、适用于现场大规模、快速筛选的免疫检测技术、多残留组分同时检测技术3个方向发展。