头孢唑林注射剂为什么要每日分次使用？

头孢唑林属于时间依赖性抗菌药物,其抗菌效果主要取决于血药浓度超过所针对细菌的最低抑菌浓度（MIC）的时间,血药浓度在体内代谢达到最高后慢慢下降,当降至无效浓度时就进行下一次用药,可尽量延长药物在体内的有效浓度时间,起到较好的治疗作用。说明书中规定本品应分次给药,目的是缩短给药间隔时间,使24小时内血药浓度高于致病菌的最小抑菌浓度时间超过60%。     

利奈唑胺血药浓度监测结果及影响因素分析

摘要：目的:对我院利奈唑胺血药浓度监测结果进行分析,探讨利奈唑胺血药浓度的影响因素。方法:回顾性收集2019年2月～2020年6月我院符合纳入标准住院患者的相关信息,采用单因素及多因素回归分析利奈唑胺血药谷浓度的影响因素。结果:73例患者中利奈唑胺平均血药谷浓度为（6.54±2.31）μg·ml-1,在参考范围内的占34.2%,低于参考范围的占12.3%,高于参考范围的占53.4%;单因素分析结果显示老年患者和肾功能不全患者利奈唑胺血药谷浓度高于非老年患者及肾功能正常患者（P＜0.05）;多因素分析结果显示利奈唑胺谷浓度随ALT和肌酐清除率的升高而降低。结论:利奈唑胺血药浓度个体差异大,肾功能不全患者进行血药浓度监测可能有助于降低不良反应发生风险。     

头孢呋辛、头孢美唑在犬胆汁中的药动学

目的 :测定头孢呋辛、头孢美唑在犬胆汁中的药动学参数 ,为临床医师提供合理使用抗生素的理论依据。方法 :在犬行胆总管造瘘的基础上 ,分别静脉注射头孢呋辛、头孢美唑各 1 g,按计划留取胆汁标本 ,微生物法测定头孢呋辛、头孢美唑在胆汁中的含量。用 3P87软件进行数据处理 ,得出有关药动学参数。结果 :头孢呋辛、头孢美唑主要的参数如峰值浓度分别为 (3 9.8±s 0 .5 )mg·L-1,(2 1 .4±0 .3 )mg·L-1,T1/ 2 分别为 (69.3± 0 .7)min,(1 0 2 .1± 1 .4)min。结论 :本组动物实验资料证明头孢呋辛、头孢美唑在胆汁中的药物浓度较作者另外观察的其他头孢类抗生素低 ,不宜作为治疗胆道感染性疾病的首选药物     

健康志愿者头孢克罗尿药浓度测定及3种制剂尿排量比较

目的:比较头孢克罗3种制剂的尿药浓度和尿排量.方法:8名健康志愿者分别单剂量po国产头孢克罗缓释片、头抱克罗普通胶囊和进口头孢克罗缓释片750mg,采用反相高效液相色谱法(RP-HPLC)测定尿中头孢克罗浓度,计算8h分段和累积尿排量及尿排百分率,用配对t检验比较3种制剂尿药浓度和尿排量.结果:国产缓释片与进口缓释片相比,相应各时间段尿药浓度无显著性差异,8h分段和累积尿排量无显著性差异;普通胶囊0～2h尿药浓度和尿排量较缓释片高,2～4、4～6、6～8h均低于缓释片,但3种制剂8h累积尿排量和尿排百分率无显著性差异.结论:缓释片维持有效尿药浓度时间比普通胶囊长.     

HPLC法测定脐带血中头孢美唑钠浓度及其在剖宫产产妇中的预防用药研究

目的:建立测定脐带血中头孢美唑钠浓度的方法,并探索头孢美唑钠作为剖宫产术前预防感染的抗生素通过胎盘的情况。方法:采用高效液相色谱(HPLC)法,色谱柱为Agilent Eclipse XDB-C18,流动相为0.026 mol·L-1醋酸铵(pH 6.0)-甲醇(85∶15),流速为1.0 mL·min-1,检测波长为273 nm。选择11例健康的剖宫产产妇,术前静脉滴注头孢美唑钠2 g,于给药后不同时间点取脐带血,用HPLC法测定其浓度。结果:头孢美唑钠血药浓度在2.5～1 000μg·mL-1范围内线性关系良好(r=0.999 4);方法平均回收率为89.6%～106.0%;日内、日间RSD均<6%。开始静脉滴注头孢美唑钠后10 min～4 h内所取脐带血,浓度范围为3.81～25.52μg·mL-1。结论:本方法简便、准确、快速、稳定性好,为头孢美唑钠临床应用及药动学研究提供了理论依据。     

美洛培南的体外抗菌活性及其在烧伤患者体内的药动学研究

目的研究美洛培南的体外抗菌活性及其在烧伤患者体内的药动学。方法采用琼脂二倍稀释法测定美洛培南对136株临床分离菌的最小抑菌浓度(MIC)。28例烧伤患者静脉滴注美洛培南0.5g,测定其不同时间的血药浓度及尿药回收率等,用3p97软件计算药动学参数。结果美洛培南对肺炎克雷伯氏菌、肺炎球菌、阴沟肠杆菌的抗菌活性强,MIC90<0.0075~0.25μg/ml。药动学参数为t1/2α(0.35±0.12)h、t1/2β(2.10±0.71)h、AUC(44.62±12.95)μg/ml、Vc(10.6±3.93)L、CLs(12.00±3.04)L/h;6.5h后平均血药浓度(1.01±0.53)μg/ml,0h~12h尿回收率(58.1±16.8)%。结论美洛培南对本试验中受试菌有很强的抗菌活性,其在烧伤患者体内的主要药动学参数与健康志愿者有较大的差异。     

美罗培南在烧伤患者的药代动力学研究

目的考察美罗培南在烧伤患者的药代动力学。方法28例烧伤患者在30min内单剂匀速静脉滴注美罗培南500mg,给药后不同时间取血和收集尿样,HPLC测定浓度,根据浓度测定结果,用3P97软件拟合药动学模型,计算药动学参数。结果研究显示,在静脉滴注0.5g美罗培南后,血药浓度-时间数据以二室模型拟合最佳,美罗培南的t1/2α为(0.35±0.12)h,t1/2β为(2.10±0.71)h,AUC为(44.62±12.95)μg·h/ml,Vc为(10.6±3.93)L,CLs为(12.00±3.04)L/h,0～12h美罗培南的尿回收率为(58.06±16.83)%。结论美罗培南在烧伤患者的主要药动学参数t1/2β、AUC、CLs、Cmax与健康志愿者有较大的差异,在12h内有约60%的原型药物从肾中消除。     

基于指南推荐的万古霉素给药方案与血药谷浓度相关性研究

目的 探讨基于指南推荐的万古霉素给药方案与血药谷浓度的关系。方法 收集某院2017年1月1日至2020年2月28日使用过万古霉素并进行药物治疗监测(TDM)的患者199例,根据监测浓度分为低谷浓度组(<10μg·mL^-1)、谷浓度组(10～20μg·mL^-1)及高谷浓度组(> 20μg·mL^-1),按照药品说明书/指南对患者的治疗方案进行评价。结果 199例患者中,低谷浓度组45例(22.6%),谷浓度组95例(47.7%),高谷浓度组59例(29.7%);按照推荐方案给药者共122例,浓度位于谷浓度组52例(42.6%)。女性的血药谷浓度显著高于男性(P <0.001),年龄<18岁组的血药浓度达标率显著低于其他年龄组(P <0.05)。结论 按照药品说明书/指南推荐的万古霉素给药方案患者血药谷浓度达标率不高,需要根据患者年龄、性别、体重、肾功能情况、合并用药、合并症制定更详细的初始给药方案,加强万古霉素的谷浓度监测并调整用药有助于患者的用药安全。     

高效液相色谱法测定头孢唑啉在人椎间盘髓核的分布

目的:建立头孢唑啉血清、髓核浓度的测定方法,观察其对人体椎间盘的渗透性。方法:10例腰椎间盘突出的患者,给予头孢唑啉2g静脉滴注30min,给药完毕后,即行手术取髓核,同时抽取静脉血,用高效液相色谱(HPLC)法测定髓核和血清的头孢唑啉浓度。结果:头孢唑啉在0.6~4.3μg·g-1及40~500mg·L-1范围内药物浓度(C)X和药物峰面积与内标物峰面积之比(A头孢唑啉/A内标)线性关系良好,血清标准曲线Y=1.7349X 0.0120,r=0.9998;髓核标准曲线Y=1.9098X-0.0088,r=0.9992。头孢唑啉在髓核中的药量分布个体差异较大,且髓核内药量与血清药浓间无相关性(r=0.122,P>0.05)。结论:本法可同时测定头孢唑啉在血清和髓核中的药物浓度,以满足临床药物监测的需要。     

RP-HPLC法测定人体液中他唑巴坦浓度及其药动学应用

目的 :建立测定体液中他唑巴坦浓度的 HPLC方法 ,并应用于哌拉西林 /他唑巴坦健康人体的药代动力学研究。方法 :10名男性健康志愿者单剂量静脉滴注 4.5 g哌拉西林 /他唑巴坦钠 ,采用反相高效液相色谱 ( RP-HPLC)法测定血浆样品和尿中他唑巴坦药物浓度。 结果 :滴注完成即刻浓度 ( cm ax)为 ( 3 4.3 3± 8.0 5 )μg/m l,清除半衰期 ( t1 /2β)为 ( 0 .94± 0 .16) h,分布容积 ( Vd)为 ( 15 .43± 3 .82 ) L/kg,清除率 ( Clr)为 ( 15 .2 0± 2 .5 4) L /h,血药浓度 -时间曲线下面积 ( AUC)为 ( 4 2 .41±7.45 ) h·μg· ml-1 。结论 :他唑巴坦的体内过程符合二室开放模型 ,他唑巴坦主要以原形经肾脏排出体外 ,8h累积尿排百分率为 ( 78.68± 5 .84) %。     

Pharmacokinetics and clinical studies of cefmetazole in the otorhinolaryngological field

Cefmetazole (CMZ), a new cephamycin preparation, has been investigated to give following results. 1) Pharmacokinetics: Serum and tonsil concentration of CMZ were determined by micropore method in humans. The mean concentrations in 5 cases about 30 minutes after administration of 0.5--1.0 g intravenously were 55.4 micrograms/ml in serum, 21.7 micrograms/g in tonsil. 2) Clinical studies: Seventy-one patients with ear, nose and throat infections were treated with CMZ receiving 1 to 6 g per day intravenously (one shot and drip infusion). Thirty-eight of 70 patients were cured excellent, 19 were good, 8 were fair and 6 were failure and effective rate was 80.3%. Adverse reaction was observed in 4 cases. Three cases showed exanthema and 1 case showed fever elevation.     

35例肾移植患者他克莫司血药浓度监测分析

目的：分析肾移植患者不同时期他克莫司血药浓度与用药量的关系,为他克莫司的使用提供参考。方法对我院2013年4月～2014年3月35例肾移植患者进行长期血药浓度监测,统计分析术后时间、用药剂量等因素与他克莫司血药浓度的关系。结果35例肾移植患者血药浓度监测共计195次,血药浓度个体差异较大。肾移植手术1个月后,他克莫司用药剂量、血药浓度较高,超过1个月后血药浓度控制在4～8ng/mL较为理想。结论他克莫司治疗窗较窄,建议服药期间进行他克莫司血药浓度监测。     

HPLC法测定体液中氨溴索浓度及其药代动力学参数

建立了 HPLC测定人血浆及尿中盐酸氨溴索含量的方法 :Hypersill C18柱 (4.6mm× 2 50 mm,5μm) ,乙腈 -甲醇 - 0 .0 1 mol/L磷酸盐缓冲液 -四氢呋喃 (35∶ 35∶ 2 7.5∶ 2 .5,V/V)为流动相 ,流速 1 .5ml/min,检测波长 2 4 2 nm。结果表明 :最低检测浓度为 5ng/ml,血药浓度在 1 0～ 32 0 ng/ml范围内线性良好 ,尿药浓度在 0 .2 5～ 8.0μg/ml范围内线性良好 ,氨溴索生物半衰期为 (4.2 1± 0 .93) h。     

影响肝移植术后环孢素A血药浓度相关因素分析

目的研究肝移植术后环孢素A(CsA)血药浓度与各生化指标、T管胆汁量及尿量的相关性。方法采用回顾性调查方法,查阅本院肝移植术后1wk~1mo内口服CsA患者病历,记录CsA血药浓度值及相应的生化检验值、T管胆汁量及尿量等数据,并应用SPSS统计软件对数据进行多元线性回归分析。结果CsA单位剂量血药浓度值与多数生化检验值间不存在明显相关性,但与胆固醇、尿素氮、T管胆汁量及尿量之间存在具有统计学意义的线性关系(P<0.01)。结论CsA血药浓度不仅受到外界因素的影响,还受患者自身体内一些因素的影响。     

Antibiotic transfer into tissue after total hysterectomy with special reference to the cefmetazole concentration of the retroperitoneal space exudate

The intent of the study was to investigate the transfer of CMZ to the retroperitoneal space exudate after hysterectomy (11 cases of simple abdominal hysterectomy and 6 cases of radical hysterectomy). Concentration of CMZ in the lymphnode was also measured in 2 cases. The results were as follows. Concentration in the retroperitoneal space exudate of CMZ after administration (intravenous drip infusion 1 or 2 g/hour) reached its peak 2 hours after administration (approximately 1 hour later than its peak in the blood). The peak level in the exudate was 1/3 to 2/3 of the peak level in the blood. After 2 hours, the concentration of CMZ in the exudate decreased gradually. The concentration of CMZ in the retroperitoneal space exudate in cases of simple abdominal hysterectomy was higher than in those of radical hysterectomy. After 1 to 3 days of radical hysterectomy, the transfer of CMZ into the exudate was as good as the transfer of that in the period immediately after operation. CMZ concentration in the lymphnode in the cases of radical hysterectomy reached 9 to 13 micrograms/mg approximately 1 hour after the start of CMZ administration (d.i. 2 g in 1 hour). Research results suggest that lymph circulation, in addition to blood stream, plays an important role in the transfer of antibiotics toward the pelvic dead space.     

Postoperative evaluation of renal function from the aspect of urinary concentration of cefmetazole in infants and children with vesicoureteral reflux and hydronephrosis. I

The urinary excretion of cefmetazole (CMZ) which was administered intravenously from both kidneys (affected side and normal side) was studied separately after surgery in 11 infants and children (10 cases of vesicoureteral reflux (VUR) and 1 case of hydronephrosis due to pelviureteric obstruction). In kidneys with VUR of grade IIb to III degree, urinary concentration of CMZ showed rather higher than that we expected from their creatinine clearance. On the contrary in kidneys with VUR of grade IV degree and hydronephrosis, urinary concentration of CMZ showed rather lower compared to their creatinine clearance.     

A nationwide study of the antimicrobial susceptibility of clinical isolates of Staphylococcus aureus in Japan

We described antimicrobial susceptibilities of clinical isolates of Staphylococcus aureus in 1985 and also a 6-year survey of changing patterns of their susceptibilities to ampicillin (ABPC), cefazolin (CEZ), cefmetazole (CMZ) and gentamicin (GM) from 1980 to 1985 in 103 hospitals. The MICs were determined by the standard method of the Japan Society of Chemotherapy. Among 2,891 isolates in 1985, ratios of resistant strains to ABPC and GM were 24% and 29%, respectively, and those to CEZ and CMZ were 8% and 3%, respectively. Gradual increases in numbers of resistant strains to ABPC, CEZ and CMZ were observed until 1984 but a trend for decreases in numbers of resistant strains to the above 3 antibiotics was observed in 1985. A continuous rise in numbers of resistant strains to GM until 1985 was noted. Isolates from clinical materials such as pus, bile, and urine showed higher incidences of resistance to ABPC and GM than those from sputum, secreta and throat swab. Rates of resistant strains to CEZ were the highest in isolates from bile, pus, sputum and urine. Rates of resistant strains to CMZ were the highest in isolates from bile, and decreased in isolates from sputum, urine and pus in this order. Rates of resistant isolates from inpatients to the 4 antibiotics tested were greater than those from outpatients.     

Basic and clinical evaluations of cefmetazole in postoperative wound infections

The time course of the concentration of cefmetazole (CMZ) in the serum and in skin and intestinal tissues was determined after a single intravenous injection of 2 g of the drug. CMZ moved into them well. Furthermore, 41 patients with postoperative wound infection (superficial in 29 and deep in 12) were treated with CMZ 2-4 g daily. Bacteriological examination of the lesions with simultaneously carried out. As a result, 101 strains of bacteria were isolated and identified. Mixed infection was found in 27 cases (65.9%). Fifteen strains (14.9%) of E. coli, 15 (14.9%) of B. fragilis, 7 (6.9%) of Klebsiella sp. and 7 (6.9%) of Proteus sp., were the main bacteria isolated. Eight cases (19.5%) had mixed infection of E. coli and B. fragilis. The committee (3 members) evaluated CMZ to be effective in 75.6% (31 of 41 cases) and bacteria disappeared in 60.5% (23 of 38 cases). The side effects observed were pyrosis and feeling of gastric malaise in 1 case. The results suggest that CMZ is useful, which exerts an excellent effect on postoperative wound infections.     

环孢霉素 A 在服药患者尿液中的含量测定简

目的 了解环孢霉素A在服药患者尿液中的含量.方法检测20例肾移植患者CsA 全血谷值浓度和尿液中CsA浓度.结果 20例肾移植患者CsA 全血谷值浓度为（73.46±15.54）μg·L-1,尿液CsA浓度为（174.83±101.52）μg·L-1.结论 CsA可以通过尿液途径部分排出体外.