Pharmacokinetics of pefloxacin and amikacin administered simultaneously to intensive care patients

Summary Ten adult patients with severe infections in an intensive care unit were treated simultaneously with 6 mg/kg pefloxacin and 7.5 mg/kg amikacin, infused i.v. over 1 h every 12 h for 5 days. Twelve h after the last infusion, pefloxacin alone was administered orally (400 mg tablet) every 12 h for 10 days. The pharmacokinetics of pefloxacin and its main metabolites, norfloxacin and pefloxacin N-oxide, were determined after the first (Day 1) and last (Day 5) infusions and after the last oral dose (Day 15). The kinetics of amikacin was determined after the first and the last infusion.The maximal and minimal steady-state plasma concentrations of amikacin were 27.3 and 3.3 mg/l. The total plasma clearance was 83.1 and 67.0 ml/min after the first and the last infusions, respectively, and the half-life was 3.9 and 5.0 h.The maximal and minimal steady-state plasma concentrations of pefloxacin were 13.1 and 7.9 mg/l after i.v. infusion and 13.4 and 9.0 mg/l after oral administration. Pefloxacin elimination (t_1/2) increased from 11.3 h after the first infusion to 19.4 h after the last infusion and 21.1 h after the last oral dose. Total body clearance decreased from 90.8 (Day 1) to 51.9 (Day 5) and 56.4 ml/min (Day 15). The volume of distribution did not change significantly over the course of pefloxacin. Mean steady-state plasma concentrations of norfloxacin and pefloxacin N-oxide were respectively 0.5–0.6 mg/l and 0.9–1.3 mg/l after intravenous and oral administration of pefloxacin.There were no pharmacokinetic interaction between the drugs. The dosage regimen led to plasma concentrations of pefloxacin and amikacin within their therapeutic range.     

家兔烧伤渗出期丁胺卡那霉素药动学

对11只正常家兔和10只20％体表面积三度烫伤后6h的家兔静脉注射丁胺卡那霉素(10mg/kg)的药动学观察表明,烫伤后6～12h的丁胺卡那霉素血浓度明显上升(P<0.001),半衰期t1/2β延长(P<0.001),中央室分布容积V_1和表观分布容积Vβ均减少(P分别<0.001和<0.02)。本实验还对1例烫伤后36h静脉注射丁胺卡那霉素的家兔进行了药动学的观察发现,烫伤后36～42h的丁胺卡那霉素血浓度较烫伤前下降,V_1和Vβ则增大。     

国产丁胺卡那霉素、卡那霉素对内耳影响的比较研究

采用组织学方法对豚鼠进行了丁胺卡那霉素耳毒性实验研究，并与对照组生理盐水和卡那霉素组进行对照。结果表明这两种药物对内耳Ｃｏｒｔｉ′ｓ器及前庭器毛细胞均有损害作用。其损害程度丁胺卡那霉素小于卡那霉素。     

丁胺卡那霉素肾毒性损害的防治研究

研究目的 探讨丁胺卡那霉素（丁卡）肾毒性损害的防治。研究方法 采用病例对比研究方法。正常对照组儿童５０例均测尿常规、尿与血β２Ｍ、尿与血ｍｏｓｍｏｌ、尿与血ＴＨＰ、尿ＡＩｂ、尿ｒＧＴ、尿ＮＡＧ、肾功能、血清丁卡浓度。研究组４３例，均为重症感染患者，其中Ⅰ组（２３例）仅用丁卡７天；Ⅱ组（２０例）丁卡、维生素Ｃ（ＶＣ）、维生素Ｅ（ＶＥ）同时用７天。Ⅰ、Ⅱ两组病例在治疗前、治疗第３天、治疗第７天均作上述     

Influence of the route of administration on the pharmacokinetics of amikacin

Summary The pharmacokinetics of amikacin was studied in 17 hospitalized patients with normal renal function (creatinine clearance greater than 90 ml/min), after the administration of a single dose of 7.5 mg/kg body weight. In 10 patients the antibiotic was administered intravenously and in the other 7 it was injected intramuscularly. After i. v. administration, the antibiotic followed an open two-compartment kinetic model, and after i. m. administration it followed a single compartment kinetic model. The route of administration did not significantly modify the pharmacokinetic parameters of amikacin. On the basis of the pharmacokinetic parameters thus established, an intravenous infusion for therapeutic use should have an administration rate of 2.5 [mg/kg/h] and a duration of 6 h.     

三种氨基苷类药物抗牵张性心律失常作用的比较

目的 研究3种氨基苷类抗生素链霉素（SM）、庆大霉素（Gen）、丁胺卡那霉素（Ami）抗牵张性心律失常的作用。方法采用膨胀体外灌流大鼠左心室，夹闭体内豚鼠升主动脉，利用标准微电极技术观察药物抗牵张性心律失常的作用和对动作电位的影响。结果SM、Gen、Ami（100-200μmol／L）能缩短心律失常的持续时间；抑制单相动作电位时程（MAPD）的缩短、后除极的产生和触发活动；抑制动作电位（AP）50％和90％复极时程的缩短，且3种药物抗牵张性心律失常作用的差异无显著性意义（P〉0．05）。结论氨基苷类抗生素能抑制牵张诱发的心律失常，主要可能的作用机制为通过阻滞牵张敏感性离子通道（SACs），抑制动作电位时程的缩短和后除极的产生。     

还原型谷胱甘肽对丁胺卡那霉素致豚鼠耳毒性作用的影响

目的：观察还原型谷胱甘肽（GSH）对丁胺卡那霉素耳蜗毒性的干预效果。方法：健康杂色豚鼠56只,随机分为4组,分别肌注丁胺卡那霉素（amikacin）、GSH、Amikacin＋GSH（联合用药）及生理盐水。各组动物在观察期结束后,检测耳蜗组织的活性氧（ROS）水平及谷胱甘肽过氧化物酶（GSH-Px）、超氧化物岐化酶（SOD）、过氧化氢酶（CAT）活力;采用耳蜗基底膜铺片的方法,对深染的外毛细胞表皮板进行计数;扫描电镜观察外毛细胞细胞器的变化。结果：丁胺卡那霉素组ROS水平增高,SOD、CAT、GSH-Px活力降低（P〈0.05）。其余3组的ROS水平均显著低于丁胺卡那霉素组（P〈0.05）,SOD、CAT、GSH-Px活力显著高于丁胺卡那霉素组（P〈0.05）,3组之间的比较各指标均无统计学意义（P〉0.05）。光镜下GSH组耳蜗三排外毛细胞呈v字型排列有序。丁胺卡那霉素组外毛细胞纤毛散乱、倒伏,深染的表皮板数明显增加,联合用药组深染的表皮板数较丁胺卡那霉素组明显减少（P〈0.01）,GSH组与生理盐水组差异无统计学意义（P〉0.05）。电镜下丁胺卡那霉素组核固缩,线粒体数量减少或大多数线粒体空泡变性;GSH组和生理盐水组细胞结构基本正常;联合用药组线粒体染色较深或轻度水肿。结论：GSH与丁胺卡那霉素联合应用可以显著地减轻丁胺卡那霉素的耳毒性。     

Appropriateness of Empiric Gentamicin and Vancomycin Therapy for Bacteremias in Chronic Dialysis Outpatient Units in the Era of Antibiotic Resistance

Abstract

Bacteremias in inpatient chronic HD units have been described, but there is little information on bacteremias in ambulatory HD units. To determine the frequency of bacteremia and pathogen distribution in ambulatory chronic HD units, we retrospectively reviewed our experience with 107 bacteremias in 5 chronic ambulatory HD units over a 3 year period. The object of the study was twofold. The first objective was to determine if bacteremias in ambulatory HD setting were substantially different in frequency or type than in the inpatient HD setting. Secondly, febrile patients suspected of having bacteremia in chronic HD patients are often empirically treated with vancomycin and gentamicin.

Chronic HD patients require repeated and frequent venous access for HD. Bacteremias are common in chronic HD patients and may be primary or secondary and are often related to venous access site infections. The distributions of bacteremia pathogens in chronic HD patients are predominantly reflective of skin flora, i.e., staphylococci and to lesser extent aerobic Gram-negative bacilli. After S. aureus (MSRA/MSSA) and coagulase-negative staphylococcus (CoNS), enterococci are the next most important Gram-positive pathogens in bacteremic HD patients. Most strains of E. faecalis are sensitive to vancomycin and for practical purposes should be considered as vancomycin sensitive enterococci (VSE). In contrast, most strains of E. faecium are resistant to vancomycin and should be considered as vancomycin resistant enterococci (VRE).

We retrospectively reviewed 107 patients on chronic ambulatory HD to determine the adequacy of empiric vancomycin and gentamicin prophylaxis. We found amikacin is preferred to gentamicin and that meropenem is an effective alternate substitution for gentamicin and vancomycin combination therapy.     

注射用阿米卡星的含量测定及与0．9％氯化钠注射剂的配伍稳定性考察

目的建立衍生化分光光度法测定阿米卡星注射剂中阿米卡星含量,并分析其在0．9％氯化钠注射剂中的稳定性。方法以乙酰丙酮-甲醛为衍生化试剂,硼酸-醋酸为缓冲液,用紫外分光光度法测定,检测波长为339nm;模拟临床用药浓度,将注射用阿米卡星0．6g加入到250mL0．9％氯化钠注射剂中,混合均匀后,在4℃和25℃下考察24h内的含量及pH值,以及观察配伍液的物理变化。结果回归方程为γ=0．5401x＋0．02327,r=0．9991,在0．2～1．5g·L^-1内吸收值与质量浓度呈良好线性关系,加样回收率98％～100％,RSD〈3％（n=5）;在4℃和25qC条件下,0～24h配伍液的外观、pH值均无明显变化。4℃条件下24h内配伍液中阿米卡星含量无明显变化,25℃条件下0～12h阿米卡星含量无明显变化,12～24h其含量降低。结论经验证,该方法简便、快速,结果准确、可靠,重复性好,适用于注射用阿米卡星中阿米卡星的含量测定;注射用阿米卡星与0．9％氯化钠注射剂配伍,在4℃时24h内稳定,25℃时12h内稳定。     

荷移-同步荧光光谱法直接测定血清中阿米卡星的含量

目的建立直接测定血清中阿米卡星含量的荷移-同步荧光光谱法。方法同步处理血清中内源激素等发射强荧光的物质,排除对阿米卡星测定的严重干扰,以分辨血清背景和阿米卡星荷移络合物的荧光信号。结果阿米卡星质量浓度在175.65～878.25μg/L范围内与荧光强度线性关系良好,检出限为33.387μg/L,回收率为95.7%～100.4%,RSD为3.5%～4.4%。结论荷移-同步荧光光谱法简单、快速、准确。