头孢菌素类药物输注时间对儿童用药安全性的影响

目的：考察5种头孢菌素类药物在5%葡萄糖注射液（GS）、0.9%氯化钠注射液（NS）和小儿电解质注射液中的稳定性,进而评价其在输液中输注时间长短对儿童用药安全性的影响。方法随机抽查本院2013年门诊儿科单月双日处方,选出5种常用头孢菌素类药物,测定其与3种注射液分别混合后的相对百分含量、pH值和外观情况,并记录患儿在输液中的输注时间。结果头孢唑肟在小儿电解质液中、头孢美唑在5%葡萄糖中、头孢呋辛在0.9%NS和5%GS中,以3 h为界其pH值有一定变化,而溶液外观、相对百分含量均无改变。头孢孟多和头孢地嗪在各时间点的溶液外观、pH值和相对百分含量均无明显变化。且各年龄段患儿的输注时间以2~3h为主。结论在3h内,这5种头孢菌素类药物的溶液外观、pH值及相对百分含量无明显变化,溶液较稳定,用于输注时间较长的儿童是安全的。     

维持性血液透析患者头孢菌素脑病7例临床分析

目的：了解维持性血液透析患者头孢菌素脑病的临床特点。方法：回顾性分析2004年4月-2012年1月我院维持性血液透析患者应用头孢菌素治疗出现的7例头孢菌素脑病的临床特征。结果：所有患者均无神经系统定位体征,血肌酐、尿素氮、电解质、血糖、血气分析、血色素等无异常,经颅脑CT或MRI检查无急性病变。6例患者经停用头孢菌素并行血液灌流治疗后症状完全消失,1例死亡。结论：维持性血液透析患者可发生头孢菌素脑病,治疗中应合理用药。     

氨噻肟唑头孢菌素的合成

本文以7-ACA为原料制备了7-ACT,再以DCC为缩合剂与侧链2(2-氯乙酰氨基噻唑-4)-(Z)-2甲氧亚胺乙酸进行缩合,使用N-甲基二硫代氨基甲酸甲胺盐脱保护基,以葡聚糖凝胶LH-20精制合成了氨噻肟唑头孢菌素;总收率35.8％。产物经~1H核磁确证为顺式构型化合物。     

Preparation and in vitro evaluation of verapamil HCl and ibuprofen containing carrageenan beads

In order to establish a method to predict oral absorption of drugs, which are absorbed by the oligopeptide transporter (PepT1), fraction absorbed (F) of cephalosporin antibiotics was predicted from in vitro uptake into rat intestinal brush border membrane vesicles (BBMV). Using in vitro uptake data, F values of cephalosporins in humans were predicted using the equation derived from the complete radial mixing (CRM) model, which was proposed by Amidon et al. (Amidon et al., J. Pharm. Sci. 69 (1980) 1369). In the present study, uptake into BBMV was measured at 25 and 4°C in the presence of an H⁺-gradient, and the uptake clearance (CL_uptake) was calculated. Clearance for the uptake mediated by PepT1 (ΔCL_uptake) was then calculated as CL_uptake at 25°C minus that at 4°C. When ΔCL_uptake and F values were analyzed according to the present equation, fairly good correlation between ΔCL_uptake and F was observed. It was further demonstrated that the present method may be able to quantitatively predict F values of cephalosporins by using several cephalosporins as standards.     

In vitro protein binding interaction studies involving cefixime

Cefixime is a new oral cephalosporin currently undergoing clinical trials. Selected agents with the likelihood for coadministration with cefixime in man were examined for their influence on the in vitro binding of cefixime in pooled serum from dog, monkey, and man. Results from these experiments showed no significant change in cerfixime binding in any animal species studied or in man by acetaminophen, heparin, phenytoin, diazepam, ibuprofen or furosemide at their maximum reported therapeutic concentrations. In contrast, both salicylic acid and probenecid resulted in concentration-dependent increases in the free fraction of cefixime (up to 2.5-fold). These findings demonstrate the usefulness of in vitro protein binding screening procedures for studying potential drug interactions that are mediated, at least in part, by changes in the protein binding of a drug.     

血液灌流联合血液透析在慢性肾衰竭患者药物性脑病中的应用

目的 探讨血液灌流(HP)联合血液透析(HD)在慢性肾衰竭患者药物性(头孢菌素)脑病中的临床疗效,以进一步指导临床治疗.方法 收集2004年9月-2011年11月收治的24例头孢菌素脑病患者,进行血液透析和(或)联合血液灌流治疗,观察两组脑病的缓解率,评定其临床效果.结果 发生头孢菌素脑病的慢性肾衰竭患者24例,12例应用HP+HD治疗,12例单纯应用HD治疗,HP+HD组完全缓解和部分缓解率分别为41.7％和58.3％,较单纯HD组缓解率高(P＜0.05),且临床症状明显改善;β2-微球蛋白(β2-MG)HP+HD组明显降低(P＜0.05),HD组降低不明显(P＞0.05).结论 在慢性肾衰竭患者中头孢菌素脑病一旦诊断应及时停药,并选择合适的血液净化方式,其中HP+HD治疗,对于分子量大或(和)蛋白结合的抗菌药物是一种较好的治疗方法.     

3-(1-甲基-5-甲硫基-1-H-四氮唑)-氨基头孢烷酸二苯基亚甲酯的合成研究

以氨基头孢烷酸为原料合成3-(1-甲基-5-甲硫基-1-H-四氮唑)-氨基头孢烷酸二苯基亚甲酯的研究,目的是通过优化反应条件,简化操作,提高产率,降低合成成本。通过对溶剂、催化剂用量、投料比、反应温度和反应液浓度等条件的优化,以两步80%左右合成收率制备3-(1-甲基-5-甲硫基-1-H-四氮唑)-氨基头孢烷酸二苯基亚甲酯。     

尿毒症患者抗生素脑病32例临床分析

目的:探讨尿毒症患者使用抗生素后脑病发生原因、临床特点、转归,提高临床医师对该病的认识。方法:回顾性分析我院2007至2010年32例尿毒症患者应用头孢菌素过程中出现脑病的临床资料,分析脑病出现前后用药情况及转归。结果:男性14例,女性18例,年龄28-76岁,原发病:糖尿病肾病14例,慢性肾小球肾炎12例,高血压肾损害4例,多囊肾2例;维持血液透析26例,未透析者6例,从开始使用到出现抗生素脑病的时间为2-10天。停用抗生素,增加透析频率后症状改善。结论:肾功能不全患者抗生素脑病的发生率逐渐增加,一旦出现中枢神经系统症状,不要单纯考虑尿毒症脑病,应警惕抗生素脑病,及时停药处理非常重要。     

In vitro andin vivo evaluations of LB10517, a novel parenteral broad-spectrum cephalosporin

Thein vitro activity of LB10517, a new catechol-substituted cephalosporin, was compared with those of E-1077, cefpirome and ceftazidime against 1034 clinical isolates collected in Japan. LB10517 showed a broad-spectrum antibacterial activity against a wide range of gram-positive and gram-negative bacteria including non-glucose fermenting rods,Pseudomonas aeruginosa. Against the methicillin-susceptible strains ofStaphylococcus aureus (MSSA) andStreptococcus pyogenes, the MIC₉₀ values of LB10517 which required to inhibit 90% of the strains were 3.13 μg/ml and 0.1 μ/ml, respectively. It was as active as E-1077 but more active than cefpirome and ceftazidime. Methicillin-resistant strains ofS. aureus (MRSA) andEnterococcus spp. were highly resistant to all the test compounds. LB10517 was highly active against most members of the familyEnterobacteriaceae, 90% of which were inhibited at a concentration of less than 0.78 μg/ml, except forEnterobacter cloacae (1.56 μg/ml) andSerratia marcescens (3.13 μg/ml). Its activity was comparable to those of E-1077 and cefpirome but it was greater than that of ceftazidime. AgainstPseudomonas aeruginosa, LB10517 showed the most potent antibacterial activity among the compounds tested. Ninety percent ofP. aeruginosa isolates were susceptible at the concentration of 0.39 μg/ml. Its activity was 32- to 128-fold higher than those of E-1077, cefpirome and ceftazidime. Against imipenem- or ofloxacinresistantP. aeruginosa, LB10517 with MIC₉₀s of 6.25 μg/ml and 3.13 μg/ml, respectively, showed 16-fold more potent activity than the other test compounds. LB10517 showed a relatively high plasma level and long plasma elimination half-life in rats (t_1/2(β), 52 min) and dogs (t_1/2(β), 103 min).