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Measuring linezolid in biological fluids using high-efficiency liquid chromatography 高效液相色谱法测定生物体液中的利奈唑胺
Pub Date : 2010-01-01 DOI: 10.1016/S2173-5085(10)70061-7
L. Guerrero , M. Sarasa , Y. López , D. Soy

Objective

Evaluation of an analytic method for determining linezolid concentrations in biological fluids including plasma, vitreous humour and cerebrospinal fluid using high-efficiency liquid chromatography and subsequent ultraviolet detection.

Method

The method was validated by studying the following parameters: accuracy, precision, sensitivity, linearity and recovery. The drug was extracted from the biological matrix by means of a protein precipitation with perchloric acid. Chromatographic separation was performed by eluting linezolid with a mobile phase consisting of 80% K2HPO4 buffer solution (15 mM; pH = 5) and 20% acetonitrile, and a stationary phase, NOVAPAK C18 150 × 3.9 mm with precolumn. The wavelength reading was 254 nm and the working flow rate was 1 ml/min.

Results

We obtained values with accuracies between 94.4% and 106.1%, and precisions between 0.88%–6% and 3.7%–5.6% for intra-and inter-day variability, respectively. Recovery obtained after analysing the plasma samples was at 93%. The method showed itself to be linear for the concentration levels under study.

Discussion

The method's behaviour can be described as linear, precise and accurate. Furthermore, the method is fast, sensitive, and inexpensive. It is useful for determining linezolid concentrations in multiple biological matrices. It can also be used as a basis for further clinical pharmacokinetic studies.

目的建立高效液相色谱-紫外检测法测定血浆、玻璃体液和脑脊液中利奈唑胺浓度的方法。方法通过准确度、精密度、灵敏度、线性度、回收率等参数对方法进行验证。用高氯酸沉淀蛋白质的方法从生物基质中提取药物。色谱分离采用流动相为80% K2HPO4缓冲液(15 mM;pH = 5), 20%乙腈,固定相NOVAPAK C18 150 × 3.9 mm,带预柱。波长读数为254 nm,工作流速为1 ml/min。结果获得的日内变异性和日间变异性的准确度分别为94.4% ~ 106.1%和0.88% ~ 6%和3.7% ~ 5.6%。分析血浆样品后获得的回收率为93%。该方法与所研究的浓度水平呈线性关系。该方法具有线性、精确、准确的特点。此外,该方法快速、灵敏、廉价。它可用于测定多种生物基质中利奈唑胺的浓度。它也可以作为进一步临床药代动力学研究的基础。
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引用次数: 0
FILNUT-scale: Rationale and use in screening for malnutrition risk within the INFORNUT process filnut量表:在INFORNUT过程中筛选营养不良风险的原理和用途
Pub Date : 2010-01-01 DOI: 10.1016/S2173-5085(10)70017-4
J.L. Villalobos Gámez , J.M. Guzmán de Damas , J.M. García-Almeida , M.M. Galindo , R. Rioja Vázquez , A. Enguix Armada , O. Bernal Losada

Objectives

To offer a rationale for assigning a minimum score for risk of malnutrition for total proteins lower than 5 g/dl and a scoring scale for our filter (FILNUT-scale); and to analyse results of the MUST screening test performed on positive scores in the FILNUT nutritional filter and assess usefulness of said test in this population.

Methods

We searched the laboratory database for laboratory test orders (dated between 2004 and 2007) for which total proteins and albumin or cholesterol levels were determined, and we identified those with results for the above three parameters plus lymphocyte count. A limit (less than 5 g/dl) was placed on the total protein level and the results for other parameters were not limited. Distribution curves for albumin and cholesterol were analysed. The same protocol was followed after establishing the CONUT score for each sample with the necessary parameters.

From September 2007 to January 2008, the MUST test was performed on all FILNUT positives and we analysed how the degrees of risk corresponded.

Results

In 95% of the cases in which total proteins are lower than 5 g/dl (n = 1,176), albumin values are between 0.98 and 2.94 g/dl, resulting in CONUT scores of 4 or 6 for albumin. Regarding total cholesterol, (n = 761) 89.1% of the samples are lower than 180 mg/dl, which accounts for one or two points in the score.

In 98.79% of the cases (n = 490) that presented all four parameters, CONUT score was ≥5, which could be classified as medium or high risk.

During the study period, 100% of the patients identified as medium or high risk by the FILNUTscale (n = 568) tested as at-risk by MUST: of these, 421 (74.1%) were at high risk and 147 (25.9%) were at medium risk.

目的:为总蛋白质低于5克/分升的营养不良风险分配最低分数和我们的过滤器评分量表(FILNUT-scale)提供一个基本原理;并分析对FILNUT营养过滤器的阳性评分进行MUST筛选试验的结果,并评估该试验在该人群中的有用性。方法我们检索了实验室数据库中测定总蛋白、白蛋白或胆固醇水平的实验室检测订单(日期为2004年至2007年),并对上述三个参数加上淋巴细胞计数的结果进行了鉴定。总蛋白水平有一个限制(小于5克/分升),其他参数的结果没有限制。分析了白蛋白和胆固醇的分布曲线。在为每个样本建立具有必要参数的CONUT评分后,遵循相同的方案。从2007年9月到2008年1月,对所有FILNUT阳性患者进行MUST测试,并分析风险程度如何对应。结果在总蛋白低于5 g/dl的病例中,95% (n = 1176)的白蛋白值在0.98 ~ 2.94 g/dl之间,导致白蛋白CONUT评分为4分或6分。对于总胆固醇,(n = 761) 89.1%的样本低于180 mg/dl,这在得分中占1到2分。在出现所有4个参数的病例中,有98.79% (n = 490)的CONUT评分≥5分,属于中危或高危。在研究期间,100%被filnutt量表(n = 568)确定为中度或高风险的患者(n = 568)被MUST测试为有风险:其中421例(74.1%)为高风险,147例(25.9%)为中度风险。
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引用次数: 2
Approach to establishing and evaluating clinical relevance of drugs interactions in HIV patients: 2009 update 建立和评估HIV患者药物相互作用临床相关性的方法:2009年更新
Pub Date : 2010-01-01 DOI: 10.1016/S2173-5085(10)70005-8
N.A. Giraldo , P. Amariles , F.J. Gutiérrez , M. Monsalve , M.J. Faus

Objective

To update information on drug interactions in patients with HIV/AIDS.

Method

PubMed was used to review English and Spanish articles published between 1 July 2007 and 30 April 2009 on antiretroviral drug interactions in humans. The search included a review of interactions between commonly-used medications in patients with HIV/AIDS and references from articles considered to be relevant.

Results

Fifty two new interactions were identified having to do with CYP3A4 metabolism and competition for intestinal absorption. New pharmacokinetic interactions were identified for medications that were already on the market, and we report interactions for drugs that were recently introduced: Tipranavir, Fosamprenavir, Darunavir, Raltegravir, Maraviroc and Etravirine.

Conclusions

There is evidence of 52 new interactions between medications using metabolic routes in the CYP450 enzymatic system, and an explanation is given for others in the intestinal absorption process.

目的了解HIV/AIDS患者药物相互作用的最新情况。方法利用pubmed检索2007年7月1日至2009年4月30日发表的关于人类抗逆转录病毒药物相互作用的英文和西班牙文文章。搜索包括对HIV/AIDS患者常用药物之间相互作用的回顾,以及被认为相关的文章的参考文献。结果共鉴定出52种与CYP3A4代谢和肠道吸收竞争有关的相互作用。新的药代动力学相互作用已经在市场上发现,我们报告了最近推出的药物的相互作用:替普那韦,福samprenavir, Darunavir, Raltegravir, Maraviroc和Etravirine。结论有证据表明,在CYP450酶系统的代谢途径中,药物之间存在52种新的相互作用,并对肠道吸收过程中的其他相互作用给出了解释。
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引用次数: 0
Application of joint analysis to ongoing training of pharmacy personnel 联合分析在药学人员持续培训中的应用
Pub Date : 2010-01-01 DOI: 10.1016/S2173-5085(10)70011-3
R. Arias-Rico

Introduction

Ongoing training by means of clinical sessions constitutes an essential activity for a pharmacy department, being joint analysis useful to adapt the clinical sessions’ characteristics to the preferences of the professionals involved. By means of this study we hope to optimize clinical sessions for their better use and efficiency.

Methods

A least squares model was used to assess the usefulness of different clinical session profiles. Data was collected from 14 individual interviews (7 specialists and 7 residents); these interviews consisted in ordering the clinical session profiles by order of preference.

Results

The most valued attributes were duration of sessions (29.9%) and the structure of teaching content (27.8%) in both groups studied; although the duration of the sessions was assigned greater value by the group of residents (31.1% vs. 27.2%). The availability of bibliographical references was the third attribute most valued (17.9%), and the two last attributes by order of importance were availability of a copy in files for storage (13.8%) and multimedia content (10.5%).

Discussion

The adaptation of clinical sessions as an integral part of ongoing training leads us to see that we can modify the duration, content structure and availability of bibliographical references so as to adapt them to the preferences of the professionals involved. However, according to the population surveyed, other attributes are of little importance

通过临床课程进行的持续培训是药学部门的一项基本活动,联合分析有助于使临床课程的特点适应所涉及的专业人员的偏好。通过这项研究,我们希望优化临床阶段,以更好地使用和提高效率。方法采用最小二乘模型评价不同临床阶段资料的有效性。数据收集自14个单独访谈(7名专家和7名住院医师);这些访谈包括按偏好顺序排列临床会议档案。结果两组学生最看重的属性是课程时长(29.9%)和教学内容结构(27.8%);尽管住院医师组认为疗程的持续时间更重要(31.1% vs. 27.2%)。参考书目的可用性是第三个最受重视的属性(17.9%),最后两个属性按重要性排序是文件副本的可用性(13.8%)和多媒体内容(10.5%)。作为持续培训的一个组成部分,临床课程的适应使我们看到,我们可以修改参考书目的持续时间、内容结构和可用性,以适应所涉及的专业人员的偏好。然而,根据接受调查的人口,其他属性并不重要
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引用次数: 1
Effectiveness and safety of 5-azacitidine in three patients with myelodysplastic syndromes 5-阿扎胞苷治疗骨髓增生异常综合征的有效性和安全性
Pub Date : 2010-01-01 DOI: 10.1016/S2173-5085(10)70014-9
M.C. Garzás-Martín de Almagro, A.I. Gago Sánchez, I. Cuevas Asencio, M. Reyes Malia

Objective

To assess the effectiveness and safety of using 5-azacitidine to treat myelodysplastic syndromes.

Methods

Review of medical records of patients who received 5-azacitidine 75 mg/m2 subcutaneously for during 7 days every 28 days in twelve cycles as compassionate use. We evaluated the objective response, clinical improvement and time to disease progression. We recorded adverse reactions described in the medical history.

Results

Six patients were candidates for treatment with 5-azacitidine. Three cases were evaluated over the study period. Most remained in partial response or better after the study, and no longer needed transfusions. In one patient, the treatment appeared to delay progression to leukaemia.

Conclusions

5-Azacitidine might be considered an effective and relatively safe drug, and may have contributed to controlling peripheral cytopenias, improving the quality of life and delaying progression to leukaemia. Additional studies with more patients are needed to support these results.

目的评价5-阿扎胞苷治疗骨髓增生异常综合征的有效性和安全性。方法对体恤用药5-阿扎胞苷75 mg/m2皮下注射7天,每28天12个周期的患者病历进行回顾性分析。我们评估了客观反应、临床改善和疾病进展时间。我们记录病史中描述的不良反应。结果6例患者适合5-阿扎胞苷治疗。在研究期间对三个病例进行了评估。大多数人在研究结束后仍保持部分缓解或更好,不再需要输血。在一名患者中,这种治疗似乎延缓了白血病的进展。结论5-阿扎胞苷可能是一种有效且相对安全的药物,可能有助于控制外周细胞减少,改善生活质量,延缓白血病的进展。需要更多患者参与的额外研究来支持这些结果。
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引用次数: 0
Assessment of a reconciliation and information programme for heart transplant patients 心脏移植患者和解与信息方案的评估
Pub Date : 2010-01-01 DOI: 10.1016/S2173-5085(10)70058-7
J. Hernández Martín , M. Montero Hernández , I. Font Noguera , L. Doménech Moral , V. Merino Sanjuán , J.L. Poveda Andrés

Introduction

The objective is to assess a pharmaceutical care programme for heart transplant patients upon patient admission and discharge.

Material and methods

Observational study of heart transplant patients, performed during the first quarter of 2007. Upon admission, the patient was interviewed regarding home treatments, adherence, allergies, and adverse effects, his/her prescriptions were compared with the last discharge report (drug reconciliation). At time of discharge, treatment was checked against the last hospital prescription (reconciliation) and an informative report was drawn up and personally delivered to the patient. Subsequently, a satisfaction questionnaire was carried out by telephone. Drug-related problems were recorded using Atefarm® software.

Results

The programme was applied to 24 patients upon admission and 23 upon discharge. No drug interactions were detected. Treatment adherence was higher than 90%. 37.5% of patients informed of an adverse reaction. Medication-related problems were identified in 16 patients (45.7%) for 6.6% of medications, most of which (38%) were for infection prophylaxis; medication omission was the most frequently-detected error. Positive evaluation of the information that was received was higher than 90%.

Conclusions

Pharmacotherapeutic follow-up upon admission and discharge resolves and prevents problems while improving patienti nformedness and satisfaction. Limitations on personnel prevent the population's requests from being met.

目的是评估心脏移植患者入院和出院时的药物护理方案。材料和方法2007年第一季度对心脏移植患者进行的观察性研究。入院时,对患者进行了关于家庭治疗、依从性、过敏和不良反应的访谈,并将其处方与上次出院报告(药物核对)进行了比较。出院时,根据最后的医院处方(核对)检查治疗情况,并起草一份资料报告,亲自交给病人。随后,通过电话进行了满意度问卷调查。使用Atefarm®软件记录与药物有关的问题。结果24例患者入院时应用该方案,出院时应用该方案23例。未发现药物相互作用。治疗依从性高于90%。37.5%的患者报告有不良反应。16例患者(45.7%)对6.6%的药物存在药物相关问题,其中大部分(38%)用于预防感染;漏药是最常发现的错误。收到的信息的正面评价高于90%。结论入院和出院时的药物治疗随访在提高患者知情程度和满意度的同时,解决和预防了问题。对人员的限制使人们的要求得不到满足。
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引用次数: 2
Cost minimisation analysis for darbepoetin alpha vs epoetin alpha in chronic kidney disease patients on haemodialysis 慢性肾病血液透析患者使用达贝泊丁与依贝泊丁的成本最小化分析
Pub Date : 2010-01-01 DOI: 10.1016/S2173-5085(10)70002-2
C. Cuesta Grueso, J.L. Poveda Andrés, J. Garcia Pellicer, E. Romá Sánchez

Introduction

Multiple studies have shown that epoetin alpha (r-HuEpo) and darbepoetin alpha (NESP) are similarly effective and safe for maintaining haemoglobin levels in patients with chronic kidney disease (CKD). Nevertheless, there is some debate over their cost-effectiveness. The purpose of this study is to carry out a cost-minimisation analysis including a comparison of the costs to the hospital arising from treatment with r-HuEpo vs NESP.

Methods

Prospective observational study. We included CKD patients on haemodialysis with no iron, vitamin B12 or folate deficiencies, treated with stable doses of IV r-HuEpo. Follow-up was performed over three periods: the first during six months, maintaining prior treatment with r-HuEpo; the second for eight months, after changing to NESP, and the third, during the final eight months, following resuming r-HuEpo treatment. For converting both treatments, the conversion factor established on technical sheet 1:200 was used.

Results

Fifty five patients completed the study and were valid for analysis. Their mean age was 68.3 years, and 18 were women (35.3%). The mean weekly doses at the end of each period were 8,058.8 (SD 3,911.1) IU for the EPO 1 period, 39.4 (SD 21.6) mg for NESP and 7,882.4 (SD 4,594.1) IU for EPO 2. The weekly costs for each treatment showed significant differences between NESP and r-HuEpo: the cost of NESP was higher.

Conclusion

In our study, we found that r-HuEpo and NESP were similarly effective in patients with CKD on haemodialysis, but that there was a significant cost increase associated with NESP treatment.

多项研究表明,促生成素α (r-HuEpo)和达贝泊汀α (NESP)在维持慢性肾病(CKD)患者血红蛋白水平方面同样有效和安全。然而,对于它们的成本效益存在一些争论。本研究的目的是进行成本最小化分析,包括比较r-HuEpo与NESP治疗对医院产生的成本。方法前瞻性观察研究。我们纳入了没有铁、维生素B12或叶酸缺乏的血液透析的CKD患者,用稳定剂量的IV r-HuEpo治疗。随访分三个时期进行:第一个时期为6个月,维持先前的r-HuEpo治疗;第二次是在改为NESP后8个月,第三次是在恢复r-HuEpo治疗后的最后8个月。对这两种处理的转化,采用技术表上确定的1:20 00的转化系数。结果55例患者完成研究,有效分析。平均年龄68.3岁,女性18人(35.3%)。每期结束时EPO 1的平均周剂量为8058.8 (SD 3911.1) IU, NESP为39.4 (SD 21.6) mg, EPO 2为7882.4 (SD 4594.1) IU。NESP和r-HuEpo的每周治疗费用有显著差异:NESP的费用更高。在我们的研究中,我们发现r-HuEpo和NESP对CKD血液透析患者同样有效,但NESP治疗的成本显著增加。
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引用次数: 3
Optimisation of a high-efficiency liquid chromatography technique for measuring lamotrigine in human plasma 高效液相色谱法测定人血浆中拉莫三嗪的优化
Pub Date : 2010-01-01 DOI: 10.1016/S2173-5085(10)70004-6
N. Rivas , A. Zarzuelo , F.G. López

Objective

The purpose of this study was to optimise the HPLC-UV bio-analytical method currently used by the Salamanca University Clinical Hospital for determining lamotrigine plasma levels.

Material and methods

The developed HPLC-UV analytic technique currently in use was shown to be linear, exact and precise, and suitable for use in routine monitoring of lamotrigine levels. The drawback of this method has always been the time required for analysing samples, so our aim was to improve on that elapsed time.

That improvement involved using a different chromatographic column from the one used up until now. We replaced the column that was normally used (Kromasil−100C18−5 μm−15*0.4 cm with a LiChroCART-RP18e−3 μm−5.5*0.4 cm); in both cases, a liquid-liquid extraction was performed and the same sample extraction protocol was followed.

Results

Both validation methods showed that the two column types are valid for routine lamotrigine monitoring.

Conclusion

The decrease in retention time, in addition to a lower quantification limit and better precision and accuracy parameters obtained with the LiChorCART column, suggest that this unit is ideal for use in clinical practice because it enables a large number of determinations to be performed in less time and the greater precision of LTG measurements.

目的对萨拉曼卡大学临床医院现行的拉莫三嗪血药浓度测定方法进行优化。材料和方法所建立的高效液相色谱-紫外分析技术具有良好的线性、准确和精密度,可用于拉莫三嗪的常规监测。这种方法的缺点一直是分析样品所需的时间,所以我们的目标是改进经过的时间。这种改进包括使用与目前使用的色谱柱不同的色谱柱。将常用色谱柱(Kromasil - 100C18 - 5 μm - 15*0.4 cm)更换为LiChroCART-RP18e - 3 μm - 5.5*0.4 cm);在这两种情况下,进行液-液提取,并遵循相同的样品提取方案。结果两种验证方法均可用于拉莫三嗪常规监测。结论LiChorCART色谱柱保留时间缩短,定量限较低,获得的精密度和准确度参数较高,可在较短时间内完成大量测定,LTG测量精度较高,是临床应用的理想选择。
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引用次数: 2
Analysis of the duration of and reasons for changing the first combination of antiretroviral therapy 首次联合抗逆转录病毒治疗的持续时间及改变原因分析
Pub Date : 2010-01-01 DOI: 10.1016/S2173-5085(10)70016-2
M.T. Martín , M. Rovira , M. Massanes , E. del Cacho , E. Carcelero , M. Tuset , C. Codina , J.M. Miro , J.M. Gatell , J. Ribas

Objective

To determine the duration of and reasons behind changing the various combinations of drugs used for the initiation of antiretroviral treatment in naïıve patients.

Methods

A retrospective observational study that included all patients with HIV infection who started antiretroviral therapy in a high-tech university reference hospital during the period from 1 January 2003 and 31 December 2005. Patients were followed until 31 December 2008. To estimate the cumulative probability of discontinuation the Kaplan- Meier method was used.

Results

A total of 441 patients were included. The average duration of the first treatment was 384 (interquartile interval 84–1290) days. The regimen based on non-nucleoside reverse transcriptase inhibitors and those that included as nucleosides abacavir or tenofovir in combination with lamivudine or emtricitabine showed a significantly longer duration than the rest. The main reasons for termination were the side effects, although in a lesser percentage than that obtained in previous studies. No associations were found between the rest of the characteristics of the patients or of the treatment and the risk of termination.

Discussion

Although the duration of the first antiretroviral treatment remains short, currently fewer changes are made due to side effects and due to loss to follow-up. The reasons may be better tolerance and less complexity. However, more studies are needed to determine the benefits of one regimen or another, and to be able to generalise the results.

目的确定naïıve患者开始抗逆转录病毒治疗时改变各种药物组合的持续时间和原因。方法回顾性观察研究,纳入2003年1月1日至2005年12月31日在某高新技术大学参考医院接受抗逆转录病毒治疗的所有HIV感染者。患者随访至2008年12月31日。使用Kaplan- Meier方法估计终止的累积概率。结果共纳入441例患者。第一次治疗的平均持续时间为384天(四分位数间隔84-1290)。以非核苷类逆转录酶抑制剂为基础的方案和核苷类包括阿巴卡韦或替诺福韦与拉米夫定或恩曲他滨联合的方案的持续时间明显长于其他方案。终止治疗的主要原因是副作用,尽管这一比例低于以往的研究。未发现患者的其他特征或治疗与终止风险之间存在关联。尽管第一次抗逆转录病毒治疗的持续时间仍然很短,但目前由于副作用和随访损失而进行的改变较少。原因可能是更好的容忍度和更少的复杂性。然而,需要更多的研究来确定一种方案或另一种方案的益处,并能够推广结果。
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引用次数: 0
Effect of pamidronate infusion time on renal function in patients with multiple myeloma 帕米膦酸钠输注时间对多发性骨髓瘤患者肾功能的影响
Pub Date : 2010-01-01 DOI: 10.1016/S2173-5085(10)70060-5
F. Sierra , E. Román , C. Barreda , M. Moleón , J. Pastor , A. Navarro

Introduction

Administration of biphosphonates in patients with renal failure requires a dosage adjustment.

Objectives

Analyse renal function evolution in multiple myeloma patients after reducing infusion time for 90 mg pamidronate by 2 h.

Methods

In 2007, a retrospective study was carried out on all patients who presented multiple myeloma and bone metastasis treated with pamidronate administered every 4 h. Following a review of the literature, a protocol for administering pamidronate every 2 h was created in partnership with Haematology, and a specific dose reduction framework was established for patients with baseline renal failure. Additionally, a prospective follow-up study of those patients’ renal function was completed to analyse its evolution after the change in infusion time.

Results

A total of six patients received 90 mg pamidronate every 4 h. 33.32% of the patients (2/6) presented baseline renal insufficiency, and therefore needed to have the pamidronate dose adjusted according to the new protocol. Subsequently, all of them received the treatment every 2 h, and one patient (16.6%) experienced altered renal function after two treatment cycles.

Discussion

Reducing administration time for pamidronate from four to 2 h did not lead to significant variations in patients’ renal function. This therapeutic practice can improve patients’ quality of life by shortening their hospital stay without aggravating their renal function.

肾衰患者使用双膦酸盐需要调整剂量。目的分析90mg帕米膦酸钠输注时间减少2小时后多发性骨髓瘤患者肾功能的变化。方法2007年,对所有接受帕米膦酸钠每4小时输注一次的多发性骨髓瘤和骨转移患者进行了回顾性研究。在回顾文献后,与血液学合作制定了每2小时输注帕米膦酸钠的方案。并为基线肾衰竭患者建立了特定的剂量减少框架。此外,我们还对这些患者的肾功能进行了前瞻性随访研究,分析其在输注时间改变后的演变情况。结果6例患者每4 h接受90mg帕米膦酸钠治疗,33.32%(2/6)患者出现基线肾功能不全,需按新方案调整帕米膦酸钠剂量。随后,所有患者每2 h接受一次治疗,1例(16.6%)患者在两个治疗周期后出现肾功能改变。将帕米膦酸钠的给药时间从4小时减少到2小时不会导致患者肾功能的显著变化。这种治疗方法可以缩短患者的住院时间,提高患者的生活质量,而不会加重患者的肾功能。
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引用次数: 1
期刊
Farmacia Hospitalaria (English Edition)
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