供应室护理缺陷分析与对策

目的：提高供应室工作质量。方法：对本院供应室1997年1月至2001年12月5年中护理缺陷发生的原因和采取的相应对策进行回顾性分析。结果：质量控制使护理缺陷发生率由0．6‰，下降至0．1‰。结论：增强质量意识，完善各项规章制度，提高护理人员的业务素质；通过质量控制，减少护理缺陷发生。     

基于PK/PD参数优化阿莫西林/克拉维酸钾缓释片给药方案

摘 要 目的：依据PK/PD参数优化阿莫西林/克拉维酸钾缓释片的临床给药方案。方法: 30名健康受试者随机分为3组,分别于空腹、餐前和餐后口服阿莫西林/克拉维酸钾缓释片,通过比较其药动学特征确定最佳给药方式。3组受试者分别单次口服低、中、高3个剂量的阿莫西林/克拉维酸钾缓释片,比较不同给药剂量下的PK/PD参数,确定给药剂量和给药间隔。结果: 阿莫西林的AUC空腹组[（32.2±15.0）μg·h·ml^-1]较餐前组[（41.7±1.92）μg·h·ml^-1]和餐后组[（42.6±17.7）μg·h·ml^-1]有所降低,而克拉维酸的AUC则是餐后组[（1.89±0.54）μg·h·ml^-1]明显低于空腹组[（2.55±0.76）μg·h·ml^-1]和餐前组[（2.58±0.76）μg·h·ml^-1]（P<0.05）。阿莫西林和克拉维酸分别在剂量1 000～4 000 mg、62.5～250 mg剂量范围内呈线性药代动力学特征。以最小抑菌浓度（MIC）为2.0 μg·ml^-1计,单次口服低、中、高剂量的阿莫西林/克拉维酸钾缓释片后,12 h内血药浓度大于MIC的持续时间（T＞MIC）分别为5.5,7,10 h,百分比分别为46%、58%和83%。以MIC为4.0 μg·ml^-1,则12 h内T＞MIC分别为4.5,6,8 h,百分比分别为38%、50%和67%。结论:给予阿莫西林/克拉维酸钾缓释片的最佳时机是在标准餐前服用,每天给药2次,每次2片即可满足T＞MIC时达到40%~50%。     

液-质联用法测定人血浆中卢非酰胺的浓度及其在药动学研究中的应用

目的:建立高效液相色谱-质谱联用(HPLC-MS/MS)测定人血浆中卢非酰胺浓度的方法。方法:40名健康受试者随机分成4组,分别单剂量口服给药卢非酰胺片200,400,800,1200 mg。血浆样品经乙腈沉淀蛋白提取分离,色谱柱为Ultimate^® AQ-C₁₈(100 mm×2.1 mm,5 μm,Welch Material Inc.);流动相为乙腈-5 mmol·L^-1乙酸胺水溶液(含0.1%甲酸)=32:68;流速为0.30 mL·min^-1;内标为埃索美拉唑。采用电喷雾离子源,以多反应监测(MRM)方式进行正离子检测。结果:卢非酰胺的血浆浓度在40~5000 ng·mL^-1范围内线性良好,定量下限为40 ng·mL^-1,日内精密度(RSD)均≤8.20%,日间精密度(RSD)均≤6.35%,提取回收率为91.94%~96.48%。卢非酰胺呈非线性药动学特征,单剂量空腹口服给药卢非酰胺片200,400,800,1200 mg后,C_max分别为1803.50±528.06, 2485.00±562.71, 3710.00±965.50和4158.00±1181.91 μg·L^-1。AUC_0-t分别为34522.13±9525.00, 56138.53±18021.98, 88848.53±23348.14和107058.03±34420.08 μg·h·L^-1。结论:该法操作简单,灵敏,准确,重复性好,适用于卢非酰胺片临床药动学研究。从药动学研究可知,卢非酰胺在中国健康受试者中呈非线性药动学特征。     

Pharmacokinetics and Tissue Distribution of Clevidipine and Its Metabolite in Dogs and Rats

The purpose of the current study was to examine the pharmacokinetic profiles and tissue distribution of clevidipine, an ultra-short-acting calcium antagonist in Beagle dogs and Sprague-Dawley rats, respectively. The pharmacokinetics and biodistribution of its primary metabolite H 152/81 were also evaluated. Dogs received intravenous infusion of clevidipine at a dose rate of 17 μg/（kg·min）, and rats were given intravenous administration of clevidipine at a dose of 5 mg/kg. Dog plasma and rat tissues were collected and assayed by HPLC-MS/MS. It was found that plasma clevidipine quickly reached the steady state concentration. The terminal half-life was short （16.8 min）, pointing out a rapid elimination after the end of the infusion. The total clearance was 5 mL/（min·kg）. In comparison, plasma concentra- tion of H152/81 was increased more slowly and was significantly higher than that of clevidipine. After intravenous administration, clevidipine was distributed rapidly into all tissues examined, with the high- est concentrations found in the brain, heart and liver. Maximal concentrations of clevidipine were found in most tissues at 10 min post-dosing. However, the proportion of clevidipine distributed in all tissues was quite small （0.042‰） compared to the total administration dose. It was suggested that clevidipine was mainly distributed in blood and it transformed to inactive metabolite raoidlv.     

左舒必利注射液在中国健康受试者的药代动力学

目的 研究左舒必利注射液在中国健康受试者单次及多次给药的药代动力学。方法 用开放、随机、平行的试验设计。30名受试者,男女各半,分为3个剂量组,分别接受单次及多次肌内注射不同剂量左舒必利,采集不同时间的血样,用高效液相色谱-串联质谱法(HPLC/MS/MS)测定血浆中左舒必利的浓度。用DAS 3.0软件计算药代动力学参数。结果 单次肌内注射25,50,75 mg左舒必利的主要药代动力学参数:cmax分别为(724.70±248.91),(949.60±234.80),(1619.00±366.80)μg·L-1;t1/2分别为(7.65±1.32),(7.58±0.89),(8.01±0.88)h,AUC0-t分别为(2874.17±1093.71),(4481.75±913.09),(7559.33±1428.87)μg·L-1·h。连续给药组t1/2为(7.41±0.79)h;AUC0-t为(4658.33±909.51)μg·L-1·h。结论 中国健康受试者单次肌内注射给药左舒必利在25~75 mg内呈线性药代动力学特征,多次给药没有蓄积倾向,男、女间比较,差异无统计学意义。