奈替米星2种给药方案治疗下呼吸道感染患者的临床疗效比较

目的　比较奈替米星2种给药方案治疗下呼吸道感染的血药浓度、临床疗效及不良反应。方法　将2 2例下呼吸道感染患者随机分为2组,日剂量(6mg·kg-1)相同,分别采用1日1次(A组)和1日2次(B组)给药,用荧光偏振免疫分析仪测定血药峰浓度及谷浓度,用数字测听仪监测听力变化,用多功能生化仪检测给药前后Cr和BUN ,比较2组临床疗效及药物不良反应。结果　奈替米星日剂量相同时,A组峰浓度显著高于B组(P <0 .0 1) ,而谷浓度(均<2mg·L-1)显著低于B组(P <0 .0 1) ;B组治疗前后Cr水平差异有统计学意义(P <0 .0 5 ) ;2组临床疗效差异无统计学意义(P >0 .0 5 )。结论　1日1次给药方案可以获得与1日2次给药方案相同的临床疗效,且药物的耳、肾毒性不变或有所降低     

31例患儿奈替米星血药浓度监测与分析

目的 :比较奈替米星 2种给药方案用于患儿呼吸道感染 ,其血药浓度与临床疗效、不良反应之间的关系。方法 :总结分析我院儿科 1999年 5月至 9月共 31例使用奈替米星的病例 ,按不同给药方法分每日 1次组与每日 2次组 ,疗程 5～ 7d。比较 2组的血药峰浓度cmax、谷浓度cmin、临床疗效及肾功能指标Cr与BUN。结果 :每日 1次组cmax=(16 5 3± 3 84) μg·mL-1,cmin=(0 2 1± 0 15 ) μg·mL-1;每日 2次组cmax=(10 0 8± 3 72 ) μg·mL-1,cmin=(0 2 9± 0 2 2 ) μg·mL-1。 2组间cmax有非常显著差异 (P <0 0 1) ,cmin则无显著性差异 (P >0 0 5 ) ;2组的有效率每日 1次组 10 0 % ,每日 2次组 87 5 % ,无显著性差异 (P >0 0 5 ) ;2组在用药前后的Cr与BUN均在正常值范围 ,且无显著性变化 (P >0 0 5 )。结论 :奈替米星应用于儿童 ,每日 1次给药疗效好、不良反应发生率低、用药方便 ,可推荐于临床应用 ,但仍需定期监测血药浓度     

奈替米星两种给药方案的临床疗效比较

目的 通过比较奈替米两种给药方案,优选其最佳给药方案。方法 血药浓度用ＴＤｘ（荧光偏振免疫法）测定。体内杀菌活性用微量稀释法测定。结果 日剂量相同时,奈替米星一天一次给药（ＯＤ）,谷浓度均低于２μｇ．ｍｌ＾－１,且较一天两次给药（ＴＤ）有显著性降低（Ｐ〈０．０５）,而其峰浓度较ＴＤ给药有显著性增高（Ｐ〈０．０１）。结论奈替米星ＯＤ比ＴＤ给药能够获得较高的峰浓度与体内杀菌活性及较低的谷浓度,有利于提     

12例COPD患者奈替米星药动学及其下呼吸道浓度测定

目的:探讨COPD老年患者奈替米星的药代动力学特性及其下呼吸道浓度分布.方法:一天一次静脉滴注奈替米星7mg/kg,以尿素作为肺泡液稀释内标,用荧光偏振免疫法测定血清、支气管分泌液和肺泡液中奈替米星浓度.结果:奈替米星7mg/kg一天一次静脉滴注30min,血清峰浓度26.71±4.95mg/L,消除半衰期3.69h;肺泡液中药物峰浓度7.76±2.13mg/L ,相当于血清峰浓度的29%,两者具有显著相关性(r=0.986),且超过常见肺炎致病菌的MIC 值;支气管分泌液药物浓度与血清峰浓度无相关性(r=0.687).结论:奈替米星一天一次静脉滴注7mg/kg用于COPD老年患者能有效治疗肺部感染.     

12例COPD患者奈替米星药动学及其下呼吸道浓度测定

目的:探讨COPD老年患者奈替米星的药代动力学特性及其下呼吸道浓度分布.方法:一天一次静脉滴注奈替米星7mg/kg,以尿素作为肺泡液稀释内标,用荧光偏振免疫法测定血清、支气管分泌液和肺泡液中奈替米星浓度.结果:奈替米星7mg/kg一天一次静脉滴注30min,血清峰浓度26.71±4.95mg/L,消除半衰期3.69h;肺泡液中药物峰浓度7.76±2.13mg/L ,相当于血清峰浓度的29%,两者具有显著相关性(r=0.986),且超过常见肺炎致病菌的MIC 值;支气管分泌液药物浓度与血清峰浓度无相关性(r=0.687).结论:奈替米星一天一次静脉滴注7mg/kg用于COPD老年患者能有效治疗肺部感染.     

大剂量奈替米星在新生儿体内的稳态药物动力学及临床疗效

目的:研究iv gtt奈替米星在新生儿体内的稳态药物动力学,观察疗效和安全性.方法:7例新生儿患者按7mg/kg.qd,iv gtt奈替米星,用药3d后用荧光偏振免疫法测定血药浓度,同时对奈替米星的抗感染效果及不良反应进行观察.结果:新生儿iv gtt奈替米星后,呈二房室动力学模型,主要药动学参数:C_(max)(18.38±5.43)μg/ml,T_(1/2β)(5.21±1.14)h.Vc(0.34±0.10)L/kg,CL(0.25±0.05)L/h,AUC(81.67±16.00)[(mg/L)·h]用药7d临床疗效满意并未发现不良反应.结论:肾功能正常的新生儿奈替米星qd iv gtt可获得较好的疗效并具有良好的安全性.     

金纳多对奈替米星致耳毒性模型豚鼠的预防和治疗作用研究

目的:研究金纳多注射液对奈替米星导致豚鼠耳毒性的预防和治疗作用。方法:将48只豚鼠随机分成生理盐水对照组、奈替米星组、金纳多预防组和金纳多治疗组,以不同方式给药4wk后,比较各组豚鼠的耳廓反射阈、脑干诱发电位、Ⅲ波时间、血清铁离子浓度和SOD活性以及耳蜗毛细胞扫描电镜图。结果:4wk后金纳多预防组和金纳多治疗组的耳廓反射阈、脑干诱发电位、Ⅲ波时间分别为(33.75±4.20)dB、(25.63±3.71)dB、(3.91±0.18)ms和(27.27±4.54)dB、(32.95±4.30)dB、(4.30±0.16)ms,2组间比较存在显著性差异(P<0.01)。结论:金纳多注射液能预防和治疗奈替米星引起的豚鼠耳毒性,而且预防给药对耳毒性的改善作用大于治疗给药。     

庆大霉素不同给药方案的药代动力学和肾功能损害的实验研究

目的研究庆大霉素(GTM)不同时辰给药方案对大鼠肾功能损害、血药浓度和药动学参数的影响。方法①大鼠分6组:对照组、时辰每日单次给药组[N(活动期给药)100组、D(休息期给药)100组,分别于1:00和13:00给药100mg·kg-1,im]、时辰每日2次不等量给药组和传统每日2次等量给药组(N90+D10组、N70+D30组、N50+D50组,每日1∶00和13∶00分2次im90mg·kg-1+10mg·kg-1、70mg·kg-1+30mg·kg-1、50mg·kg-1+50mg·kg-1)。各组分别于给药d1、10和20测定血清肌酐(Cr)、血清尿素氮(BUN)。②给药后0.25、0.5、1、2、5和8h分别于眼眶取血,测定血药浓度,给药d10、20重复上述采血过程。绘制药时曲线,计算药动学参数。结果①肾功能损害:给药d10,N50+D50组Cr和BUN水平最高,与给药d1和同期对照组相比差异有显著性(P<0.05);N100组最低,与同期对照组相比差异有显著性(P<0.05)。血药浓度:给药d10,N100组和D100组峰浓度差异有显著性(P<0.05)。给药d20,N50+D50组峰浓度高于两次不等剂量组峰浓度,但差异无显著性。③药动学参数:给药d20,N50+D50组CLs最小,N100组最大,给药d1、10、20,N100组T12最短,N50+D50组T12最长(P<0.05)。结论在时辰给药方案中,GTM以活动期单次给药肾功能损害最小,血药峰浓度低,T12最短,CLs最大。     

奈替米星治疗中风病人肺部感染疗效评价

目的　评价奈替米星治疗中风合并肺部感染病人的临床效果和安全性。方法　 12 0例中风合并肺部感染病人随机分为两组 ,奈替米星组 62例 ,男性 3 4例 ,女性 2 8例 ,年龄 ( 64± 8)岁 ,用硫酸奈替米星葡萄糖注射液 4mg·kg-1·d-1,静脉滴注 ,每天 1次或 2次 ,疗程 7～ 10d。头孢曲松钠组 5 8例 ,男性 3 1例 ,女性 2 7例 ,年龄( 64± 8)岁 ,用头孢曲松钠粉针剂 ( 2 0～ 4 0 ) g/d加入氯化钠注射液 2 5 0ml,静脉滴注 ,每天 1次或 2次 ,疗程 7～10d。结果　两组疗效、细菌清除率和不良反应发生率差异均无显著性 (P >0 0 5 )。结论　奈米替星用于治疗中风合并肺部感染病人疗效确切 ,使用安全     

头孢拉定对奈替米星药代动力学的影响

目的 观察头孢拉定对奈替米星药代动力学的影响。方法 14例感染患随机分成单用奈替米星组（NTM）和奈替米星＋头孢拉定组（NTM＋CPR）。采用高效液相色谱－间接光度检测（HPLC－IPD）法，测定患单剂量静脉滴注5mg NTM后的血清药物浓度，并计算主要药动学参数；同时测定尿液药物浓度及药物回收率。结果 NTM组和NTM＋CPR 的T1／2β分别为2.40±1.01h和4．33±1．43h(P<0.01),AUC0-24h 63.42±30.00mg/L·h和78．54±32．88mg/L·h(P<0.01)，24h尿中NTM回收率也有显性差异。结论 NTM＋CPR联用时NTM生物利用度增高，尿中回收率下降，连续长期联用将导致体内蓄积。     

Comparison of non-kinetic and kinetic approaches to individualization of gentamicin dosage

Summary A prospective study was carried out in 40 acutely ill patients to compare the non-kinetic and kinetic approaches to individualization of the dosage regimen of gentamicin. The patients were divided into two equal groups. For the non-kinetic group, the doses were derived from the physician's personal experience, on a mg/kg basis, and by use of nomograms. The total daily dose ranged from 1.43 to 4.5 mg/kg. Based on serum concentration measurements, the dosage regimen for individual patient was calculated by Sawchuk-Zaske's method. The calculated doses were compared to the prescribed doses in each patient. Of the patients on empirically prescribed doses 65% received 36% more drug than the calculated dose and 20% received 36% less than the calculated dose. The calculated dosing intervals were greater than the recommended intervals in 60% of the patients. The gentamicin trough concentration was > 2 g/ml in 70% of the patients. There was a significant tendency to overdosage of the patients.For the kinetic group, following administration of the calculated dose, the steady-state peak and trough concentrations in each patient were measured. The correlation of measured to predicted steady-state serum concentrations was excellent (r=0.9968, p<0.05). About 85% of the served trough concentrations and 90% of the peak values fell within the therapeutic range. The mean of the prediction error (ME), mean absolute error (MAE), mean squared error (MSE), and root mean squared error (RMSE) of the trough and peak concentrations were calculated. The 95% confidence interval of the ME for the trough and peak concentrations included zero, which shows that the prediction was not significantly biased.A significant relationship between gentamicin clearance and the ratio of the peak and trough concentrations achieved to the administered dose (r=0.873, 0.916 for trough and peak, respectively) was found.The findings suggest that the individualized approach to dosage determination using pharmacokinetic principles, in conjunction with daily monitoring of serum gentamicin concentrations, may provide safe and effective therapy.     

Toxic serum trough concentrations after administration of nebulized tobramycin

The goal of administering nebulized antibiotics is to provide patients with a high concentration of drug at the infection site with minimal systemic effects. In two studies in which nebulized tobramycin 300 mg twice/day was administered, systemic peak concentrations were below 0.2 and 3.62 microg/ml, and trough concentrations were undetectable, making toxicity from this route of administration negligible. A 19-year-old woman who received a heart transplant was administered tobramycin inhalation solution for Acinetobacter baumanii pneumonia; her serum trough concentrations were found to be toxic (> 2.0 microg/ml). Her risk factors for experiencing these toxic concentrations were renal failure and administration of the drug by positive pressure ventilation. Although nebulized tobramycin is safe under routine circumstances, clinicians must be aware of its potential for toxicity in patients with renal dysfunction or in those receiving positive pressure ventilation.     

地高辛治疗窗浓度的再探讨

目的:探讨地高辛治疗慢性心力衰竭的血清治疗窗浓度范围。方法:将心力衰竭患者随机分成小剂量组和常规剂量组,分别给予小剂量和常规剂量地高辛治疗,采用荧光偏振免疫法测定地高辛血药浓度。结果:小剂量组有效率、无效率、中毒率分别为71.9%、21.9%、6.3%,常规剂量组分别为64.7%、19.1%、16.2%,2组有效率、无效率均无显著性差异(P>0.05),中毒率小剂量组显著低于常规剂量组(P<0.05);小剂量组地高辛有效、无效、中毒浓度分别为(0.87±0.41)、(0.67±0.34)、(1.70±0.48)μg/L,常规剂量组分别为(1.11±0.48)、(0.71±0.39)、(1.69±0.63)μg/L,2组地高辛无效浓度、中毒浓度均无显著性差异(P>0.05),地高辛有效浓度小剂量组显著低于常规剂量组(P<0.01)。结论:地高辛治疗慢性心力衰竭的血清治疗窗浓度范围以0.50～1.50μg/L为宜。     

肾移植术后长期应用硫氮唑酮对环孢素A用量和肾功能的影响

目的:观察钙通道阻滞药硫氮唑酮(Dil)长期应用对肾移植受者环孢素A(CsA)用量和肾功能的影响。方法:将Dil用于67例服用CsA的肾移植受者,以同期59例肾移植受者为对照,调整2组CsA血药浓度在治疗窗范围内,观察2组用药后36mo内CsA用量以及血肌酐变化。结果:术后第12、24、36moDil组每例CsA用量较对照组同期平均少14353、9656、7817mg;术后12mo内2组血肌酐无显著性差异,以后对照组血肌酐水平上升较快,术后18mo～36mo,Dil组血肌酐水平明显低于对照组同期(P<0.05)。结论:肾移植术后长期应用Dil不仅可明显减少肾移植受者的CsA用量,而且可以改善移植肾功能。     

血清药理学方法观察复方斑蝥胶囊对人肝癌细胞SMMC-7721增殖的影响

目的 :研究复方斑蝥胶囊含药动物血清对人肝癌细胞SMMC -7721增殖的影响。方法 :采用血清药理学方法 ,对兔灌胃给予不同剂量 (临床等效剂量、2倍临床等效剂量和3倍临床等效剂量 )的复方斑蝥胶囊混悬液 ,应用MTT比色法观察含药血清对人肝癌细胞SMMC -7721增殖的抑制作用 ,同时观察临床等效剂量组各采血时间点的抑制作用。结果 :3个剂量组的含药血清对SMMC -7721细胞增殖均有抑制作用 (P<0 01) ,其中以3倍临床等效剂量组含药血清的抑制率最高 ;临床等效剂量组各采血时间点的含药血清对SMMC -7721细胞增殖均有抑制作用 (P<0 05) ,其中3h时含药血清的抑制率最高。结论 :复方斑蝥胶囊含药动物血清对人肝癌细胞SMMC -7721增殖具有一定的抑制作用 ,并具有剂量依赖性。     

荔枝核皂苷改善地塞米松致大鼠胰岛素抵抗作用机制研究

目的 :研究荔枝核皂苷改善地塞米松 (DX)致大鼠胰岛素抵抗 (IR)的作用机制。方法 :采用DX诱导制作IR大鼠模型 ,观察荔枝核皂苷对模型鼠给药2h后空腹血清血糖 (FSG)、总胆固醇 (TC)、三酰甘油 (TG )、皮质醇 (Cortisol)、胰岛素含量及胰岛素敏感指数 (ISI)等指标的影响。结果 :荔枝核皂苷能显著降低模型鼠FSG、TC、TG含量 ,显著提高ISI值 (P<0 05或P<0 01)。结论 :荔枝核皂苷可改善DX所致糖、脂代谢障碍 ,降低模型鼠中血皮质醇及胰岛素水平 ,改善其胰岛素敏感性。     

左氧氟沙星治疗老年患者下呼吸道感染的疗效分析

目的 :评价左氧氟沙星治疗老年患者下呼吸道感染的临床疗效及安全性。方法 :选择下呼吸道感染老年患者66例 ,随机均分为治疗组和对照组。治疗组选用左氧氟沙星注射液0 4g ,静脉滴注 ,1次/d ,疗程7d～14d ;对照组选用氧氟沙星注射液0 4g ,静脉滴注 ,1次/d ,疗程7d～14d。结果 :治疗组、对照组有效率分别为90 9 %、66 7 % (P<0 05) ;细菌阴转率分别为93 9 %、87 9 %(P>0 05) ;不良反应发生率分别为9 1 %、33 3 % (P<0 05)。结论 :左氧氟沙星治疗老年患者下呼吸道感染安全、有效。     

侵袭性真菌感染患者采用伏立康唑静脉和口服给药对血药浓度和临床疗效影响的对比分析

目的：比较侵袭性真菌感染患者采用伏立康唑静脉和口服两种给药途径对血药浓度、临床疗效以及安全性的影响。方法：选取2021年9月 ~ 2023年3月就诊于东部战区总医院并接受伏立康唑治疗的侵袭性真菌感染患者，按给药途径分为静脉组和口服组，比较两组的血药浓度、临床疗效和安全性。结果：研究纳入104例患者进行分析，共收集231例伏立康唑血药浓度。静脉组的稳态谷浓度平均值略高于口服组，差异无统计学意义[（3.44 ± 2.45）mg·L-1 vs （2.90 ± 2.55）mg·L-1，P ＞ 0.05]，两组间的目标浓度达标率相近（71.70% vs 76.80%），但静脉组高于目标范围上限的比例大于口服组（22.64% vs 12.80%）。两组之间的临床有效率和总体药物不良反应发生率相近，差异无统计学意义（68.75% vs 77.78%，P ＞ 0.05；40.62% vs 52.38%，P ＞ 0.05）。结论：侵袭性真菌感染患者使用伏立康唑静脉给药的血药浓度有大于口服给药的趋势，但两组间的目标浓度达标率，以及临床疗效和安全性均无统计学意义上的差异。     

A comparison of the pharmacokinetics of two dosing regimens of cisapride and their effects on corrected QT interval in premature infants

OBJECTIVE: To compare the pharmacokinetics of two dosing regimens of cisapride and their effects on QT(c) interval. DESIGN: Thirty-one pre-term infants were enrolled in two neonatal intensive care units. In 16 infants, cisapride was started at 0.2 mg/kg orally every 6 h (group A) and in 15 infants at 0.1 mg/kg orally every 3 h (group B). Electrocardiograms were performed before and after 72 h of treatment to calculate the QT(c) interval according to the Bazett formula. After 72 h of treatment, cisapride and norcisapride trough concentrations, and concentrations 1 h after the next cisapride administration were quantified in serum. A linear regression analysis was performed to analyse the effect of postnatal and postconception age. RESULTS: At the start of cisapride treatment, mean postnatal age was 22.9+/-13.9 days (mean+/-SD) for group A and 23.3+/-15.0 days for group B, and mean postconception age was 34.0+/-1.8 weeks for group A and 33.3+/-0.8 weeks for group B. The QT(c) interval increased equally in both groups (group A: +37+/-20 ms, and group B: + 38+/-25 ms; P=0.9). Mean concentration of cisapride 1 h after administration was, as expected from the dosing regimen, significantly higher in group A than in group B (123.7+/-43.2 ng/ml versus 86.7+/-27.8 ng/ml; P=0.03).The difference in trough concentration was not significant (107.4+/-44.3 ng/ml versus 78.2+/-35.4 ng/ml; P=0.09). There was a positive correlation between QT(c) prolongation and cisapride serum concentration (peak: R(2)=0.20, P=0.015; trough: R(2)=0.24, P=0.008) and an inverse correlation between postnatal age and concentration 1 h after administration concentration of cisapride (R(2)=0.19, P=0.02). No correlation was found for postconception age. CONCLUSION: Postnatal age has an inverse relationship with cisapride serum concentration in premature infants, whereas postconception age is not correlated. The maturation process of the biotransformation system of cisapride during the first weeks of life, triggered by birth, but independent of gestational age at birth can explain this observation. The effect of cisapride on cardiac repolarisation is positively related with the cisapride serum concentration. Administering cisapride every 3 h instead of every 6 h could be advantageous, as it is associated with lower peak cisapride serum concentrations. Further investigations are required to confirm this and its potential clinical benefit on QT(c )and arrhythmia risk.     

1 018 例癫痫患儿丙戊酸钠血药浓度监测及影响因素分析

目的:分析癫痫患儿丙戊酸钠(VPA)血药浓度的监测结果,为临床用药提供依据。方法:采用高效液相色谱法测定1 018例癫痫患儿的VPA血药浓度,分析年龄、性别、给药剂量和药物剂型等因素对VPA血药浓度的影响以及VPA血药浓度与疗效之间的关系。结果:癫痫患儿VPA血药浓度低于治疗窗的528例(51.9%),位于治疗窗内的464例(45.6%),高于治疗窗的26例(2.6%)。年龄、性别和给药剂量对VPA血药浓度的影响差异有统计学意义(P < 0郾05),药物剂型对VPA 血药浓度的影响差异无统计学意义(P>0.05),VPA血药浓度与疗效之间存在统计学差异(P<0.05)。结论:VPA血药浓度个体差异大,且受癫痫患儿年龄、性别和给药剂量等因素影响,为实现个体化药物治疗,应常规监测血药浓度。