OCT1基因rs2282143 rs628031和rs36056065多态性对二甲双胍药代动力学的影响

目的 探讨有机阳离子转运体1（OCT1）基因中 rs2282143（P341L ,1022C＞ T）、rs628031（M408V ,1222A＞G）和rs36056065（ins/del GTAAGTTG）多态性对二甲双胍药代动力学的影响。方法 65例男性健康自愿者空腹口服盐酸二甲双胍片500 mg ,采用液相色谱-串联质谱法测定血浆中二甲双胍的浓度,并根据rs2282143、rs628031和rs36056065多态性进行分组。结果 rs2282143多态性中CC、C T 和 T T分别为45例（69．2％）、19例（29．2％）和1例（1．5％）,CC 和 CT 组间的 Cmax 、Tmax 、AUC0-t 、AUC0-∞和 T1/2差异无统计学意义（P＞0．05）。rs628031与rs36056065等位基因完全连锁,其中 AA/ins、AG/ins-del 和 GG/del 分别为8例（12．3％）、24例（36．9％）和33例（50．8％）。AG/ins-del的Cmax 、AUC0-t 、AUC0-∞显著高于 AA/ins和GG/del ,差异有统计学意义（P＜0．05）,AA/ins和GG/del之间差异无统计学意义（P＞0．05）;Tmax 、T1/2在3种基因型间差异无统计学意义（P＞0．05）。结论 rs2282143多态性与二甲双胍药代动力学无相关性,完全连锁的 rs628031和 rs36056065与二甲双胍药代动力学密切相关。     

降压新药尼群洛尔片药代动力学研究的临床观察和护理

目的 探讨降压药物药代动力学研究中临床观察和护理的作用。方法 24名健康受试者分为尼群地平组、阿替洛尔组和尼群洛尔组,每组8人。观察3组健康受试者服药前和服药后的坐位、立位和卧位血压和心率变化以及任何不适主诉和体征,通过静脉留置针采得药代动力学研究的血液样本。结果 与尼群地平组和阿替洛尔组比较,尼群洛尔组的健康受试者服药前和服药后坐位、立位和卧位收缩压和舒张压以及心率均未有显著性差异。通过密切观察未发现尼群洛尔组的健康受试者有不良反应。结论 药代动力学研究中临床观察对降压药物安全性的评估是重要的,规范的护理操作和整体护理对药物临床试验的顺利完成起到重要的作用。     

甲磺酸加替沙星片健康人连续给药药代动力学

目的 :研究健康人口服甲磺酸加替沙星片连续给药后药代动力学 ,为该药Ⅱ期临床试验提供依据。方法 :8名受试者服用甲磺酸加替沙星片 2 0 0mg ,每日 1次 ,连续 7d。以高效液相色谱法 (HPLC)测其血清、尿药物浓度。结果 :受试者口服甲磺酸加替沙星片后 ,人体耐受良好 ,体内过程符合二室开放模型。第 1天和第 7天的血药浓度达峰时间 (Tmax)分别为 1.2 2h和 1.35h ,高峰血药浓度 (Cmax)分别为 1.94mg/L和 2 .0 2mg/L ,血消除半衰期 (t1/ 2 β)分别为 6 .4 8h和 7.89h ,药时曲线下面积 (AUC0 ∞)分别为 2 0 .5 4mg·h/L和 19.81mg·h/L ,给药后 2 4h内尿药累积回收率为 5 9.86 %。 结论 :甲磺酸加替沙星片具有良好的药代动力学特征 ,每日 2 0 0mg 1～ 2次口服可用于治疗敏感菌感染。     

塞克硝唑胶囊健康人体生物等效性研究

目的研究塞克硝唑胶囊在健康志愿者中的生物等效性。方法21名男性健康志愿者随机交叉单次空腹服用试验制剂塞克硝唑胶囊和参比制剂塞克硝唑片剂。用高效液相色谱法测定血清中塞克硝唑的药物浓度。结果受试者单剂口服1000mg塞克硝唑试验药和对照药后,主要药动学参数Cmax分别为(22.69±3.60)和(23.29±3.62)mg/L;Tmax分别为(1.18±0.49)和(1.15±0.65)h;t1/2β分别为(26.43±5.77)和(27.08±5.46)h;AUC0-t分别为(701.12±123.89)和(709.93±89.06)mg·h/L;AUC0-∞分别为(761.14±147.96)和(773.71±108.23)mg·h/L。试验制剂对于参比制剂的平均相对生物利用度AUC0-∞为(98.38±12.83)%。结论受试者单剂空腹给药后塞克硝唑在体内的过程符合二室模型,AUC0-t、AUC0-∞及Cmax经统计学处理,表明试验制剂塞克硝唑胶囊和参比制剂塞克硝唑片具有生物等效性。     

健康人国产加替沙星片的药代动力学

目的 :研究健康人口服加替沙星片后药代动力学特征。方法∶10名健康受试者单剂口服加替沙星片 2 0 0mg ,反相高效液相色谱法 (HPLC)测其血清、尿药物浓度。结果∶受试者单剂口服加替沙星片 2 0 0mg后 ,人体耐受良好 ,体内过程符合二室开放模型。药物口服后迅速吸收 ,达峰时间短 ,tmax为 (1.0 8± 0 .38)h ,血cmax为 (1.0 8± 0 .18)mg/L ,AUC0 -∞ 为 (9.0 1±0 .15 )mg·h/L ,V/Fc值为 (133.0 3± 36 .39)L/ 5 5kg。消除半衰期平均为 (7.84± 1.83)h ,48h尿累积回收率为 (6 2 .3± 8.0 )%。结论∶加替沙星口服吸收良好 ,血峰浓度高于敏感菌MIC值 ,组织分布广 ,2 0 0mg每日 1～ 2次口服可用于治疗常见敏感细菌感染。     

盐酸伐昔洛韦在人体内的药动学和相对生物利用度

目的研究伐昔洛韦在正常人体内药动学和相对生物利用度。方法20名健康志愿者单剂量交叉口服伐昔洛韦300mg和参比片，用高效液相色谱（HPLC）法检测受试者血药浓度，并计算两者的药动学参数。结果受试药与参比药的血药浓度水平一致。其主要药动学参数t1/2分别为（3．81±0．66）h和（4．15±0．74）h；Tmax分别为（1．48±0．58）h和（1.38±0．56）h，Cmax分别为（1．86±0．50）mg／L和（2．07±0．62）mg／L，AUC分别为（7．51±1．71）mg·h／L和（7．03±0．98）mg·h／L，两制剂的药动学参数相近。用AUC估算的伐昔洛韦试验药相对生物利用度为98．0％±11．8％。结论伐昔洛韦片和参比片的AUC、Cmax经方差分析和双向单侧t检验表明两制剂生物等效；Tmax经非参数法检验表明两种制剂差异无统计学意义（P〉0.05）。     

国产辛伐他汀片的生物等效性

目的建立高效液相色谱-质谱联用法测定血浆中辛伐他汀浓度的方法,经方法学验证其灵敏度、专属性、线性范围、精密度、准确度、稳定性和介质效应等。方法120名男性健康受试者分两组进行单剂量二交叉试验,测定天津药业焦作有限公司研制的辛伐他汀片相对于杭州默沙东制药有限公司生产的辛伐他汀片的生物利用度。单剂量口服辛伐他汀试验片（10mg／片,4片）及辛伐他汀参比片（20mg／片,2片）后,测定辛伐他汀的血药浓度经时过程,并计算试验制剂和参比制剂的主要药代动力学参数。结果Cmax分别为（6．2±2．8）ng／mL和（6．0±2．6）ng,／mL,Tmax分别为（1．8±0．6）h和（1．8±0．5）h,t1／2分别为（3．4±1．1）h和（3．2±1．1）h,MRT分别为（5．2±1．2）h和（5．3±1．3）h,AUC0-14分别为（21．6±8．8）（ng·h）／ml和（21．6±8．9）（ng·h）／ml,AUC0-14分别为（23．4±9．0）（ng·h）／ml和（23．3±8．9）（ng·h）／ml;按AUC0-14计算,试验制剂中辛伐他汀片的相对生物利用度为（100．5±10．4）％;AUC和Cmax经对数转换后方差分析检验,Tmax经Wilcoxon符号秩检验,表明差异均无统计学意义。结论将AUC和Cmax对数转换后经双单侧t-检验表明,试验制剂和参比制剂生物等效。     

甲磺酸帕珠沙星注射液在健康人体的药动学及药效学研究

目的:研究甲磺酸帕珠沙星注射液的药代动力学及药效学特点.方法:筛选健康受试者12名,单次及多次静滴甲磺酸帕珠沙星注射液,用反向高效液相色谱-紫外法测定血药浓度及尿药浓度,用DASver1.0软件拟合药代动力学参数.结果:甲磺酸帕珠沙星体内过程符合二室模型;单次给药后的药代动力学参数:Tmax为0.47±0.09 h,Cmax为13.71±1.81 mg/L,AUC0-t为24.60±4.15 mgh/L,T1/2为1.46±0.64 h.Q 12 h静滴帕珠沙星500 mg连续5日,第2、3、4、5日晨测得的谷浓度分别为0.13、0.16、0.17、0.14 mg/L,提示血药浓度已达稳态.末剂给药后的药代动力学参数:Tmax为0.48±0.10 h,Cmax为15.41±1.67 mg/L,AUC0-t为28.42±4.90 mg*h/L,T1/2为1.33±0.49 h,(Css)av为2.34±0.43 mg/L,DF为99.48±0.38%,以上参数与单次给药比较除Cmax外差异均无统计学意义,且累积系数小,说明本品多次给药无体内蓄积.女性和男性受试者主要药动学参数比较均无统计学意义.本品对临床大多数常见致病菌的AUC0～24 h/MIC＞ 100且Cmax/MIC＞8.受试者给药期间未出现严重不良反应.结论:500 mg Q 12 h静滴,在人体内可达到有效血药浓度,可作为临床应用的推荐方案.     

克林霉素磷酸酯片在中国健康志愿者的药物代谢动力学

目的：研究克林霉素磷酸酯片在中国健康志愿者的药物代谢动力学。方法：24名健康志愿者,男女各半，随机分为3组,每组8人，男女各半，分别口服合肥恒星药物研究所研制的克林霉素磷酸酯片300、600、900mg，进行人体药代动力学试验。用高效液相紫外检测方法测定血清克林霉素磷酸酯的浓度，将所测得的血药浓度时间数据，采用3P97程序在计算机上进行分析,根据F值与AIC选择房室模型，求算药代动力学参数。结果：口服300、600、900mg克林霉素磷酸酯片的主要药代动力学参数分别为：T1/25km（h）：1．95±0．25，1．91±0．22，2．17±0．22；Tmax（h）：1．00±0．13，0．91土0．13，0．97土0．16；Cmn（μg／mL）：4．05±0．86，5．79±0．62，7．51±1．44；AUC0-9（μg·h／mL）：12．99±2．62．17．32±1．61，23．66±4．30。结论：本品口服吸收快，消除慢。24名健康志愿者口服克林霉素磷酸酯片后的经时血药浓度变化过程，均符合一级吸收的一房室模型     

尼扎替丁分散片与尼扎替丁普通片在健康人体内的药代动力学研究

目的比较尼扎替丁分散片与尼扎替丁普通片在健康人体内药代动力学行为。方法 12名男性健康志愿者均分为2组,分别单剂量口服尼扎替丁分散片与尼扎替丁普通片150 mg,用高效液相色谱法检测尼扎替丁的血药浓度。结果尼扎替丁分散片与尼扎替丁普通片主要药代动力学参数Cmax分别为(1614.8±106.2)μg/L和(1 311.7±89.5)μg/L,tmax分别为(1.0±0.6)h和(1.5±0.4)h,t1/2分别为(4.8±1.3)h和(5.3±1.1)h,AUC0∞分别为(4731.3±118.29)μg/(h.L)和(4518.6±108.3)μg/(h.L),AUC0t分别为(2216.7±106.9)μg/(h.L)和(2187.4±78.9)μg/(h.L)。结论尼扎替丁分散片的tmax、t1/2明显小于普通片,Cmax又明显高于普通片,说明尼扎替丁分散片具有良好的速释效果。     

Identifying Injection Drug Users at Risk of Nonfatal Overdose

Objectives: Drug overdose is the second leading cause of accidental deaths among U.S. adults aged 15–64 years. Emergency physicians have a unique opportunity to provide overdose prevention interventions, because habitual drug users are in frequent need of medical care. The authors evaluated associations between individual-level risk factors and experiencing an overdose in the past six months to determine which characteristics and behaviors may be most predictive of overdose.
Methods: The authors used data from a sample of street-recruited habitual drug users who participated in face-to-face interviews about overdose from November 2001 to February 2004. This analysis was restricted to 772 respondents who had been injecting for at least one year and who had injected heroin within the past two months.
Results: A total of 16.6% of participants had overdosed in the past six months. Characteristics and behaviors that were independently associated with an increased risk of a recent overdose were having had a prior overdose (odds ratio [OR], 28.58; 95% confidence interval [CI] = 14.10 to 57.96), using cocaine/crack in the past six months (OR, 2.07; 95% CI = 1.25 to 3.45), using alcohol in the past six months (OR, 1.90; 95% CI = 1.01 to 3.57), experiencing serious withdrawal symptoms in the past two months (OR, 2.70; 95% CI = 1.58 to 4.61), and younger age.
Conclusions: Drug users who have previously experienced a nonfatal overdose are at very high risk of experiencing future overdoses. Further longitudinal studies are needed to identify robust predictors of overdose risk over time in habitual drug users, but these data suggest that drug users who have overdosed warrant aggressive prevention efforts such as agonist maintenance treatment or provision of take-home naloxone.     

抗心律失常药导致室性心律失常187例临床分析

目的分析抗心律失常药导致室性心律失常的原因。方法应用动态心电图分析187例抗心律失常药致室性心律失常。结果各种抗心律失常药都有不同程度致心律失常不良反应,尤其Ic类抗心律失常药致室心律失常作用较强。结论当左室射血分数降低(LVEF40%),联合应用利尿剂及/或地高辛,和/或应用抗精神类药物,用药后QT间期离散度增加等都可出现致室性心律失常不良反应。     

635株鲍曼不动杆菌的分布及耐药性分析

目的分析南京第一医院鲍曼不动杆蒯的分布及对抗菌药物的耐药情况,指导临床合理用药。方法时南京第一医院2006年10月至2009年5月检出的635株鲍曼不动杆菌的分布及药敏结果作回顾性分析。结果共分离到革兰阴性非发酵菌2472株,其中鲍曼不动杆菌635株,占25．69％,是非发酵菌中仅次于铜绿假单胞菌位于第2位的感染菌,标本主要来源于痰液（85．04％）,病房集中于ICU（51．34％）。该菌对头孢哌酮／舒巴坦的敏感性较高,而对其他抗菌药物耐药严重,并出现多重耐药的菌株。结论南京第一医院鲍曼不动杆菌所占比例越来越大,应定期监测其分布和耐药情况,为临床合理使用抗菌药物提供依据。     

1641株临床分离病原菌的分布及耐药分析

目的了解重庆市涪陵中心医院2006～2008年临床分离病原菌的分布情况及常见细菌的耐药现状。方法对2006～2008年临床科室送检的培养标本,采用MicroScan A/s-4自动细菌鉴定及药敏测试仪进行鉴定和药敏试验,并对其结果进行统计分析。结果 4621份标本共分离出的病原菌占34.93%,其中以革兰阴性杆菌为主。检出前5位的病原菌依次为大肠埃希菌、铜绿假单胞菌、肺炎克雷伯菌、金黄色葡萄球菌、鲍曼不动杆菌。送检标本主要以痰、血液、脓、尿液为主。耐甲氧西林的金黄色葡萄球菌(MRSA)的检出率为55.74%;产超广谱β-内酰胺酶(ESBLs)的大肠埃希菌和肺炎克雷伯菌的检出率分别为36.55%、26.38%;铜绿假单胞菌和鲍曼不动杆菌是多重耐药菌株,对多种抗菌药物耐药。结论本院分离的细菌耐药水平高且多重耐药,加强病原菌的耐药性监测,有利于合理使用抗菌药物和减缓多重耐药菌株的形成。     

Drug Design and Discovery: Translational Biomedical Science Varies Among Countries

Drug design and discovery is an innovation process that translates the outcomes of fundamental biomedical research into therapeutics that are ultimately made available to people with medical disorders in many countries throughout the world. To identify which nations succeed, exceed, or fail at the drug design/discovery endeavor—more specifically, which countries, within the context of their national size and wealth, are “pulling their weight” when it comes to developing medications targeting the myriad of diseases that afflict humankind—we compiled and analyzed a comprehensive survey of all new drugs (small molecular entities and biologics) approved annually throughout the world over the 20‐year period from 1991 to 2010. Based upon this analysis, we have devised prediction algorithms to ascertain which countries are successful (or not) in contributing to the worldwide need for effective new therapeutics.     

An analysis and comparison of commonly available United Kingdom prescribing resources

Background and objective: Safe prescribing requires accurate and practical information about drugs. Our objective was to measure the utility of current sources of prescribing guidance when used to inform practical prescribing decisions, and to compare current sources of prescribing guidance in the UK with idealized prescribing guidance. Methods: We developed 25 clinical scenarios. Two independent assessors rated and ranked the performance of five common sources of prescribing guidance in the UK when used to answer the clinical scenarios. A third adjudicator facilitated review of any disparities. An idealized list of contents for prescribing guidance was developed and sent for comments to academics and users of prescribing guidance. Following consultation an operational check was used to assess compliance with the idealized criteria. The main outcome measures were relative utility in answering the clinical scenarios and compliance with the idealized prescribing guidance. Results: Current sources of prescribing guidance used in the UK differ in their utility, when measured using clinical scenarios. The British National Formulary (BNF) and EMIS LV were the best performing sources in terms of both ranking [mean rank 1·24 and 2·20] and rating [%excellent or adequate 100% and 72%]. Current sources differed in the extent to which they fulfilled criteria for ideal prescribing guidance, but the BNF, and EMIS LV to a lesser extent, closely matched the criteria. Discussion: We have demonstrated how clinical scenarios can be used to assess prescribing guidance resources. Producers of prescribing guidance documents should consider our idealized template. Prescribers require high‐quality information to support their practice. Conclusion: Our test was helpful in distinguishing between prescribing resources. Producers of prescribing guidance should consider the utility of their products to end‐users, particularly in those more complex areas where prescribers may need most support. Existing UK prescribing guidance resources differ in their ability to provide assistance to prescribers.     

联合采用降压药物治疗原发性高血压病的临床意义

目的:探讨单剂与联合应用降压药物对高血压患者血压的影响及临床意义。方法:选取正在口服抗高血压药物至少1 个月以上的高血压病患者380例,按服用单剂(EH1组,212例)和联合用药(EH2组,168例)进行分组,对比分析血压控制情况及降压有效率。单独分析31例高血压合并糖尿病患者的血压控制情况。结果:EH2组的降压有效率(83.9%)明显高于EH1组(56.6%,P<0.005);EH2组的平均收缩压与舒张压均低于EH1组(P<0.001);服用单剂降压药物无效而改为增加药物剂量的患者,其血压降低均值明显小于改为联合用药的患者(P<0.01);31例高血压病合并糖尿病的患者降压有效率仅为35.5%,并且多为联合用药的患者。结论:小剂量联合应用抗高血压药物的降压效果明显优于单剂药物,单剂药物效果不明显而改为联合用药的降压效果明显优于单剂药物增加剂量的效果。     

Trends in carisoprodol abuse and misuse after regulatory scheduling: a retrospective review of California poison control calls from 2008 to 2015

Background: In January 2012, carisoprodol was classified as a Schedule IV substance under the controlled substances act from a previously non-controlled, non-scheduled classification. Carisoprodol is marketed as a skeletal muscle relaxant and is commonly cited for its abuse potential.

Objectives: We aimed to compare volume of calls involving carisoprodol abuse or misuse to a statewide poison control system before and after the scheduling change.

Methods: Data were extracted from poison control calls coded as “misuse/abuse” involving carisoprodol from four years before (2008 to 2011) and four years after (2012 to 2015) the scheduling change. The volume of calls from pre- and post-scheduling change was compared after adjusting for yearly California census data.

Results: The number of calls related to carisoprodol abuse or misuse was significantly decreased in the four years following the change compared to the four years before.

Conclusion: Scheduling of carisoprodol was temporally related to decreased exposures as reported to California Poison Control Centers. Governmental regulation may impact a drug’s potential for abuse.     

256株非发酵菌临床分布和耐药性分析

目的了解医院感染常见非发酵菌的临床分布和耐药情况。方法常规方法进行细菌培养和鉴定,用kirby-Bauer法进行体外药物敏感试验。结果 256株非发酵菌中分离率居前3位的依次为铜绿假单胞菌占51.6%,不动杆菌属占18.0%,嗜麦芽寡养单胞菌占10.2%,铜绿假单胞菌耐药率为6.8%~70.0%,对亚胺培南、哌拉西林/他唑巴坦、头孢他啶、头孢吡肟、阿米卡星耐药率低;不动杆菌属的耐药率和铜绿假单胞相似;嗜麦芽寡养单胞菌耐药率为19.2%~84.6%,对哌拉西林/他唑巴坦、头孢他啶、头孢吡肟耐药率低,其他均存在较高耐药率。结论铜绿假单胞菌、不动杆菌属、嗜麦芽寡养单胞菌是引起医院感染主要的非发酵菌,对多种抗菌药物存在高耐药率,应加强临床病原学检测,根据药敏结果合理用药,减少医院感染发生。