Comparative study on pharmacokinetics of Cephradine in diabetic and normal rats

Objective To study effects of diabetes mellitus(DM)on pharmacokinetics of cephradine(CED)by comparing the difference in pharmacokinetic behaviours of CED between diabetic and normal rats.Methods DM was induced in male rats by a single iv injection of alloxan 60 mg·kg-1;rats whose blood glucose was over 16 mmol·L-1 were taken as DM group.The rats were divided into DM group and normal control(CTL)group,which were subdivided into low dose(90 mg·kg-1)and high dose(180 mg·kg-1)subgroups.CED was administered by iv or po routes.Blood samples collected at different time post dosing were analyzed by RP-HPLC to yield CED plasma concentration time course.Chromatographic separation was achieved on a Kromasil C18 column(250×4.6 mm ID,5 μm);mobile phase,consisting of 0.025 mol·L-1 KH2PO4-MeOH-CH3CN(87;6∶7 v/v),was delivered at 1.0 mL·min-1;UV detector was set at 261 nm.The peak area ratio of CED to cephalexin(CEX)as internal standard vs concentraion of CED was used to construct calibration curve.50 μL aliquots of TCA-deproteined plasma samples were injected into chromatograph.Results The methodology validation including specificity,precision,accuracy,recovery,limit of quantitation,linearity,stability,etc.,showed that the HPLC assay developed by us completely met requirements of pharmacokinetic study Both DM and CTL groups showed the two-compartment model for iv dosing and extravascular one-compartment model for po dosing as well as first-order kinetics.However,in iv experiment,DM group,when compared with CTL group,presented a significantly shortened t1/2β and MRT as well as increased CL,reflected by t1/2 β 84-91 vs 116-120 min,MRT 61-70 vs 103-119 min;CL 23-25 vs 18-19 mL·min-1·kg-1(P<0.05);in po experiment,a markedly shorter t1/2 K and tmax as well as greater CL and Cmax in DM group than in CTL group were found;meanwhile,DM rats suffered from remarkably increased kidney weight(KW)and KW/BW ratio relative to CTL rats.Conclusions DM pathological status can speed up elimination of CED from body of rats;the compensatory hypertrophy and thereby hyperfunction of kidneys in early-stage diabetics may explain in part at least this accelerated elimanation.     

清凉止嗽汤治疗外感久咳120例

为探讨中药治疗外感久咳的方法,将200例患者分为两组治疗组(120例),给予清凉止嗽汤;对照组(80例),给予头孢拉定和甘草合剂.结果两组总有效率分别为93.4%、73.7%,其中的治愈率分别为88.4%和41.3%;治愈病例疗程分别为(4.0±1.0)d、(5.0±2.0)d.两组比较有统计学意义(P＜0.05～0.001).     

头孢拉定不良反应的meta分析

目的 系统评价拉氧头孢及其对照药物在治疗感染时不良反应的发生率。方法 由2位研究者分别独立检索中国知网、万方数据库、维普期刊数据库、中国生物医学文献数据库、PubMed、Embase、Cochrane Library等数据库自建库至2018年3月有关头孢拉定及其不良反应的临床随机对照试验文献,严格按照纳入与排除标准筛选文献,评价文献质量并提取相关数据,采用RevMan 5.3软件进行meta分析,试验序贯分析（trial sequential analysis,TSA）软件进行TSA。结果 共纳入符合条件文献50篇,总计7 477例患者。Meta分析以及TSA结果显示：①头孢拉定组与对照组在不良反应发生率上差异具有统计学意义[RR=0.62,95%CI（0.54,0.72）,P<0.000 01]。②适应证亚组分析中呼吸道感染亚组中,头孢拉定组与对照组在不良反应发生率上差异具有统计学意义[RR=0.66,95%CI（0.53,0.80）,P<0.000 1],其他适应证因样本量过少未予分析。③对照药物亚组分析结果显示,头孢拉定组不良反应发生率高于阿奇霉素、头孢克肟、头孢克洛3组,而低于阿莫西林/克拉维酸组,仅阿奇霉素组差异具有统计学意义[RR=0.44,95%CI（0.28,0.70）,P=0.000 5],同时,TSA结果表明证据确切。④剂量亚组分析结果显示超剂量组[RR=0.70,95%CI（0.54,0.91）,P=0.008]与常规剂量组[RR=0.61,95%CI（0.52,0.71）,P≤0.000 01]不良反应发生率差异均具有统计学意义。结论 头孢拉定不良反应的发生率明显高于对照药物组,故临床用药时应严格按照说明规定用量进行用药,警惕其不良反应的发生。     

A medusa-like β-cyclodextrin with 1-methyl-2-(2′-carboxyethyl) maleic anhydrides,a potential carrier for pH-sensitive drug delivery

Abstract

We developed a new pH-sensitive drug delivery carrier based on β-cyclodextrin (β-CD) and 1-methyl-2-(2′-carboxyethyl) maleic anhydrides (MCM). The primary hydroxyl groups of β-CD were successfully attached to MCM residues to produce a medusa-like β-CD–MCM. The MCM residue was conjugated with cephradine (CP) with high efficiency (?>?90%). More importantly, β-CD–MCM–CP responded to the small pH drop from 7.4 to 5.5 and released greater than 80% of the drugs within 0.5?h at pH 5.5. In addition, the inclusion complex between β-CD–MCM–CP and the adamantane derivative was formed by simple mixing to show the possibility of introducing multi-functionality. Based on these results, β-CD–MCM can target weakly acidic tissues or organelles, such as tumours, inflammatory tissues, abscesses or endosomes, and be easily modified with various functional moieties, such as ligands for cell binding or penetration, enabling more efficient and specific drug delivery.     

HPLC法同时测定头孢拉定和精氨酸的含量

以ＨＰＬＣ外标法同时测定注射用头孢拉定（含精氨酸）中头孢拉定、精氨酸和杂质头孢氨苄的含量。方法;采用ＳｐｈｅｒｉｓｏｒｂＣ１８柱,乙腈－醋酸盐缓冲液（１２：８８）为流动相,检测波长２００ｎｍ。结果：该法能罗好地分离被测组分和有关杂质,被测组分的线性关系良好,回收率满意,结论：该法专属性好,快速,准确。     

奥格门丁与头孢拉定随机对照治疗细菌性感染

奥格门丁(Augmentin)是棒酸(Clavulanic acid)与羟氨苄青霉素(Amoxicillin)的复方制剂,内含羟氨苄青霉素1.0g,棒酸0.2g。本组所用奥格门丁静脉注射针剂为英国比切姆公司原粉,由华北制药厂生产提供。本组试验共治疗细菌性感染42例。其中16例试验药奥格门丁与对照药头孢拉定(Cephradine)16例进行随机对照临床试验,两组临床痊愈显效率分别为87.5%与81.3%,细菌消除率分别为83.3%与81.3%;奥格门丁共观察26例(开放10例,随机对照16例),临床痊愈显效率为88.5%,细菌消除率为85.7%,不良反应发生率15.38%。     

口服头孢拉定在血透病员中的药物动力学及给药方案

本文报道4倒尿毒症病员进行血透治疗时口服500mg头孢拉定,透析期内病员体内及透析器的药物动力学参数分别为V_B0.11±0.06和1.1±1.5L/kg;CL0.040±0.024和0.16±0.20L/(kg·h);t_(1/2)1.90±0.26和9±5h。5h透析病员体内药量下降64％,透析器可清除41％药物。表明头孢拉定能被透析清除。3例病员血透前口服500mg头孢拉定的血浓峰值为52.91μg/ml,血透后再给500mg补充剂量,在再次给药前血浓值仍有51μg/ml。     

超重力法制备超细头孢拉定抗生素药物及其特性

 目的　制备超细头孢拉定结晶颗粒,以提高产品质量。方法　用超重力法制备了超细头孢拉定粒子;利用TEM,BET,TG,XRD和FTIR等分析方法分析现有工业化产品和超重力法制备产品的特性。结果　证明超重力法结晶的头孢拉定产品和常规法结晶产品比,粒径减小;但都是无水结晶头孢拉定,晶型也相同。结论　由于其粒度减小,BET比表面积增加,XRD衍射半峰宽变宽。不加助溶剂时,超重力法获得的头孢拉定通针性、混悬效果、溶出速率及溶解度要明显优于常规法产品。     

新生儿静脉滴注头孢拉定的药代动力学

 本文对15名新生儿进行了单次静脉滴注头孢拉定50mg/kg后的药物动力学研究,并对8名新生儿进行了尿药浓度测定?其结果为静滴头孢拉定50mg/kg后峰浓度为84.30±28.00mg/L,药物消除半衰期为 1.91±0.56h,表观分布容积为 0.76±0. 28L/kg,清除率为 0.322±0.126L· kg^-1· h-1?本文还对不同日龄新生儿药物消除?情况进行比较,结果表明:日龄大于 14d比不足 14d的新生儿消除半衰期缩短,清除率增加,差异有显著性?静滴后8h尿药浓度达105.8±61.75mg/L?     

头孢拉定－乙基纤维素微囊的研制

以乙基纤维素为包囊材料，采用油中干燥法制备了头孢拉定微囊，并对微囊的含量、粒度分布及释放速度等进行了研究。