辛伐他汀治疗肾移植术后高脂血症患者

目的 研究辛伐他汀对肾移植术后高脂血症患的疗效。方法 17例肾移植术后患每日口服辛伐他汀10mg，持续时间1个月。口服辛伐他汀前后患自肘静脉采血，以标准酶法在自动生化分析仪上测定血浆总胆固醇、甘油三酯浓度，并以特异性荧光偏振免疫法测定环孢素全血药物浓度。结果 17例肾移植术后患在口服辛伐他汀每日10mg一个月后，血浆总胆固醇水平从8.47±2.18mmol/L显降至7.59±3.28mmol/L(P<0.05），而甘油三酯水平基本不变，环孢素全血浓度从185.31±39.02ng/ml显升高至257.33±57.78ng/ml（P＜0.01），在口服辛伐他汀的21例患无1例观察到严重药物不良反应。     

肾移植术后患者血栓调节蛋白测定的临床意义

目的 研究肾移植术后患血栓调节蛋白（TM）测定的临床意义。方法 采用ELISA法测定19例肾移植术后患中TM值。结果 肾移植术后正常组患血浆中TM值显低于环孢素肾毒性组和急性排斥组患血浆中TM值，而环孢素肾毒性组环孢素血药浓度水平显高于术后正常组和急性排斥组。结论 TM测定对鉴别环孢素毒性和急性排斥反应可能有临床价值。     

影响老年高血压病患者用药依从性原因分析

目的：了解影响老年高血压病患用药依从性原因，制定护理对策；方法：采用问卷调查方法，对102例老年高血压病患进行调查，分析影响用药依从性原因；结果：102例老年高血压病患中，住院期间87．3％能按时遵医嘱服药，出院后仅5．9％能按时遵医嘱服药，其余94．1％都不同程度存在着用药不规范、不坚持的现象。结论：须改善医疗各个环节，提高用药依从性，以提高患生存质量。     

“七彩药盒”在艾滋病抗病毒药物治疗中的应用

目的增强艾滋病患者抗病毒治疗的服药依从性,改善患者生活质量,延长生命,避免二代传播。方法利用"七彩药盒",将一周所服用的药物分装在7组药盒中,并标注早、中、晚,按时服用药物已达到有效避免漏服和服用错误现象的发生。结果七种颜色,七组药盒有效避免了漏服和错服发生。结论帮助病人建立良好的服药依从性和服药习惯,有效地解决了漏服和服用错误的问题,服药依从性达到100%,保证了抗病毒治疗有效性。     

地尔硫zhuo对环孢素A肾毒性的防护及血药浓度的影响

目的：了解肾移植术后患应用地尔硫zhuo对环孢素A（CsA)血药浓度的影响及肾保护作用。方法：选用25例肾移植患分两组，治疗组加用地尔硫zhuo，采用荧光偏振免疫分析法测定CsA的全血谷浓度。结果：治疗组CsA的用量明显低于对照组，地尔zhuo能降低尿酸、血清肌酐、尿素氮水平。结论：地尔硫zhuo能减少CsA用量，防护CsA肾毒性，还可减少患费用。     

特异性和非特异性荧光偏振免疫法测定全血环孢素的…

对２０位肾移植术后病人的４１份环孢素（ｃｙｃｌｏｓｐｏｒｉｎ）血样，用美国Ａｂｂｏｔｔ公司的荧光偏振免疫分析法即单克隆全血环孢素测定法（ＳＴＤｘ）和全血环孢素豚其代谢物测定法（ＮＳＴＤｘ）进行测定，所得资料用统计学ｔ检验和线性回归分析进行处理。结果显示：服药后８ｈ和１２ｈ体内环孢素原型率有非常显著差异（Ｐ＜０．００１），它们分别为４６％（８ｈ）和３０％（１２ｈ）。在两方法测定结果之间有较好相关性（     

中青年肾移植者合用环孢素A和百令胶囊后血生化指标的三维图像

目的：研究中青年肾移植者合用环孢素与百令胶囊后全血环孢素A的浓度变化及对血6项生化指标的影响。方法：将40～59岁的中年患者（n=219）和小于40岁的青年患者（n=145）的合用环孢素A与百令胶囊天数、百令胶囊剂量、全血环孢素A浓度、红细胞计数（RBC）、血红蛋白（Hb）、白蛋白（ALB）、总胆固醇（TC）、三酰甘油（TG）与血糖（Glu）共9项指标分为3组：（合用药物天数＋全血环孢素A浓度＋百令胶囊剂量）组，（RBC＋Hb＋ALB）组，（TC＋TG＋Glu）组，采用MATLAB7．0软件分别绘制中年和青年组的三维图像，分析图像特征并对比分析中年组与青年组的图像异同。结果：三维图像显示出各项指标间存在内在关系与个体差异。结论：环孢素与百令胶囊的合用天数对中、青年肾移植患者的血6项生化指标有不同影响。     

HPLC法测定环孢素胶囊中环孢素及降解产物的含量

用HPLC法，ODS柱，水-四氢呋喃-0．4mol/L磷酸正丙胺溶液（0．4mol/L王丙胺溶液，用磷酸调pH值为2．6）（590:400：10）为流动相；柱温：70°C；检测波长：220nm，测定环孢素胶囊中环孢素及降解产物的含量。在248～1982ug/ml浓度范围内，环孢素浓度与峰面积线性关系良好，r=0．9999。环抱素的回收率为99．9％，RSD=0．21％（n=6）。环孢素及降解产物的含量测定结果与采用瑞士Novartis公司方法所得结果相符。     

我院门诊患者用药依从性调查

目的 了解我院门诊患者用药依从性现状．提出改善用药依从性意见。方法 采用问卷调查法．对150例门诊患者用药依从性等问题进行调查。结果 患者中存在用药不依从性占59％．其中，同时存在2种以上不依从性表现形式的占47％。用药不依从性的表现形式主要是：过早停止服药（46％）、漏服（4l％）、服药时间错误（39％）。结论 针对引起用药不依性的原因．提出改善意见．发挥药物治疗效果。     

采用MATLAB分析1000例肾移植患者手术年代、年龄与服药例数三维数据图像

目的：分析肾移植患者的手术年代、年龄、服药例数以及老年患者服用环孢素的时间、剂量与血药浓度的三维图像。方法：采用MATLAB软件，针对本院1986—2004年的肾移植手术情况，按年份、年龄、患者的服药例数与60岁以上肾移植患者术后服用环孢素的天数、用药剂量、血药浓度两组数据做三维图像可视化处理。结果：1000例患者服药数据信息及49例老年患者用药信息在三维图像中体现。结论：从图像上可直接获得肾移植服药例数及老年患者的用药相关信息。     

Potential utility of electronic drug compliance monitoring in measures of adverse outcomes associated with immunosuppressive agents

Poor compliance with prescribed medications limits the effectiveness of many pharmacologic therapies and enhances their potential toxicities. Traditional methods of measuring drug-taking behavior, including direct observation, patient self-report, pill counts, and therapeutic drug level monitoring, all have well-described limitations in validity and interpretability. Electronic medication event monitoring has been used to assess compliance with therapies for hypertension, glaucoma, anemia, and epilepsy, overcoming many problems of traditional approaches. However, no published reports describe the use of electronic monitoring with immunosuppressive agents, despite their increasing use for non-life-threatening conditions and their many dose-dependent toxicities. Transplant recipients are thought to be at particular risk from noncompliance. Therefore, we undertook this study to assess the feasibility of electronically monitoring compliance with immunosuppressive drugs among renal allograft recipients. Twenty-five kidney transplant patients receiving immunosuppressive medications from a single pharmacy were enrolled. Each subject received electronic monitors with their immunosuppressive serum drug refills for cyclosporine and azathioprine. Each subject returned their monitors after the first month of this 2-month study for downloading data. The frequency distribution of interdose intervals were described. Two measures of average non-compliance were calculated for both drugs: the proportion of monitored days that had missed doses, and the proportion of missed doses. Once daily and twice daily regimens of cyclosporine were compared. Concordance in drug compliance between the two drugs was calculated for each subject and averaged over the study population. Twenty-two of 25 subjects missed one or more doses of cyclosporine or azathioprine. Seventeen (68%) subjects never missed four or more consecutive doses. Subjects were non-compliant with cyclosporine on 8.7% of monitored days, and non-compliance with azathioprine on 9.8% of monitored days. Subjects were non-compliant with 6.8% of their cyclosporine doses and 9.8% of their azathioprine doses. Patients were compliant with both drugs on 86.6% of days and were non-compliant with both drugs on 5.1% of days. Subjects were non-compliant with cyclosporine during 5% and 13.2% of monitored days for once and twice daily dosing regimens, respectively. Concordance analysis demonstrated that for 91.7% of days of monitoring, compliance information was identical for both drugs. This study demonstrated the feasibility of electronic medication event monitoring among kidney transplant patients. This methodology represents an important tool for monitoring compliance of immunosuppressive agents essential to their safe and effective use, and should be considered for use in future studies of these drugs and others with substantial dose-dependent toxicity.     

Compliance and medication knowledge among elderly Japanese home-care recipients

Objectives: To investigate the risk factors for noncompliance in elderly home-care recipients; and to evaluate to what extent regular home visits and drug counseling by a pharmacist contribute to compliance. Subjects: One hundred and sixty-three elderly home-care recipients aged 62 years and over took part in this study. All subjects were cognitively normal, and taking a regimen of one or more prescribed drugs. Medication use was observed by pharmacist-conducted interviews during home visits. Compliance was estimated by comparing prescribed regimens with medications actually being taken at home. Results: The mean age with (SD) of the subjects was 78.7 (8.3) years. Eighteen per cent were regularly counseled by a pharmacist about medication. Poor compliance with prescribed medications was associated with subjects aged 80 years and over, who were administering their own medication, consuming less than three meals a day, did not have one dose packages, and who were not receiving pharmacist counseling. In multiple logistic regression analyses, frequency of meals (OR 5.99; 95% CI 1.25–28.79), pharmacist counseling (OR 5.32; 95% CI 2.00–14.20), and age (OR 0.96; 95% CI 0.92–1.00) were independent predictors of good compliance for home-care recipients with physical disabilities. Compliance correlated inversely with knowledge of drug names, and drug purposes in the uncounseled group. Compliance, however, positively correlated with knowledge of drug purposes in the counseled group. Conclusion: In this study, compliance among elderly Japanese home-care recipients was found to be associated with receiving pharmacist counseling, frequency of meals, and age. Received: 22 June 1998 / Accepted in revised form: 2 December 1998     

泊沙康唑对异基因造血干细胞移植受者环孢素血药浓度的影响

目的:探讨异基因造血干细胞移植(allo-HSCT)受者体内泊沙康唑对环孢素血药浓度的影响.方法:纳入27例allo-HSCT受者,采用环孢素免疫抑制治疗且血药浓度位于治疗窗(150～300 μg·L-1)内,之后合用泊沙康唑预防真菌感染.收集受者合用泊沙康唑前与合用1～10 d内的环孢素谷浓度(C0)、浓度剂量比(C...     

Effects of calcineurin inhibitors on sirolimus pharmacokinetics during staggered administration in renal transplant recipients

STUDY OBJECTIVE: To compare the effects of different calcineurin inhibitors on sirolimus pharmacokinetics during long-term, staggered administration in kidney transplant recipients. Design. Randomized, open-label, parallel-group trial. SETTING: A medical center and one of its teaching hospitals in Taiwan. PATIENTS: Twenty-two de novo kidney transplant recipients. INTERVENTION: Patients received cyclosporine microemulsion or tacrolimus capsules twice/day in combination with once-daily sirolimus solution and corticosteroids. Sirolimus was administered 6 hours after the morning dose of cyclosporine or tacrolimus. After receiving a 6-mg loading dose of sirolimus, participants received sirolimus 2 mg/day for at least 7 days. Neither the cyclosporine nor the tacrolimus dosage was adjusted for at least 3 days before and during blood sampling for pharmacokinetic profiling. MEASUREMENTS AND MAIN RESULTS: One patient dropped out because of trimethoprim-sulfamethoxazole-related hepatotoxicity. We observed no differences between the two patient groups in terms of their demographic data, renal and liver function, or dosage of sirolimus during the study. During multiple-dose administration, the area under the whole-blood concentration-time curve and the peak and trough concentrations of sirolimus in the cyclosporine group were, respectively, 1.46 (95% confidence interval [CI] 1.21-1.71), 1.42 (95% CI 1.08-1.76), and 1.42 (95% CI 1.09-1.76) times higher than those of the tacrolimus group, even though sirolimus was administered 6 hours after the other agents. CONCLUSION: Sirolimus pharmacokinetics may change significantly when calcineurin inhibitors are switched, even with staggered administration, which may not completely prevent a drug interaction between cyclosporine and sirolimus solution.     

肾移植术后患者苯那普利与环孢素相互作用的探讨

为肾移植术后患者合理应用抗高血压药物提供依据。方法：采用ＦＰＩＡ法测定环孢素全血药物浓度，６例肾移植术后患者在合并应用苯那普利前、合用７ｄ后、停药后第７天，分别测定血清肌酐、尿素氮、环孢素血药浓度、血压。结果：患者合并用苯那普利前、后的血清肌酐、尿素氮、环孢素血药浓度经统计学检验无显著性差异（Ｐ＞０．０５），合并用药后血压较合并用药前有显著下降（收缩压降低Ｐ＜０．０１，舒张压降低Ｐ＜０．０５）。结论：苯那普利与环孢素合并用药时能对抗环孢素相关性高血压，但对患者的肾功能无不良影响，且基本不改变环孢素的血药浓度。     

Clinical and Medicoeconomic Impact of the Cyclosporine-Diltiazem Interaction in Renal Transplant Recipients

The effect of the diltiazem-cyclosporine interaction on cyclosporine pharmacokinetics, pharmacodynamics, and pharmacoeconomics was studied in 10 recipients of renal allografts. Each subject was studied while receiving diltiazem 60 mg twice/day and while not taking the drug. After achieving steady-state conditions, cyclosporine and metabolite concentrations were determined in whole blood from samples drawn after the morning cyclosporine dose. After pharmacokinetic analysis, all patients were followed for 6 months during treatment with cyclosporine plus diltiazem or cyclosporine alone. Cyclosporine blood clearance decreased significantly after treatment with diltiazem (18.0–11.0 ml/minkg; p=0.008). The apparent volume of cyclosporine distribution also decreased significantly (4.26–2.62 L/kg; p<0.05). After 6 months, diltiazem had no effect on renal function indexes, and no apparent effect on immunosuppression. Alterations in cyclosporine clearance and apparent volume of distribution secondary to diltiazem result in dosage reduction and potential cost savings in transplant pharmacotherapy. The mean decrease in cyclosporine dosage requirements would produce a cost saving of $1520 or 28% per patient per year.     

环孢素对肾移植术后患者血脂影响的浓度依赖性(英文)

研究环孢素对血脂影响的浓度依赖性。方法对16例肾移植术后患者测定术前和术后血脂及环孢素血药浓度。结果在环孢素血药浓度与术后术前血浆胆固醇及甘油三酯差值之间无统计学相关性。但术后血浆胆固醇的增加在高浓度患者中具有统计学显著性(P>0.05)。结论环孢素对肾移植术后患者血脂的影响呈浓度依赖性。     

Sex differences in response to cyclosporine immunosuppression in experimental kidney transplantation

1. Female donors and recipients have increased risk of acute rejection and subsequent chronic allograft nephropathy (CAN), especially when cyclosporine A (CsA) is used. Decreased renal nitric oxide (NO) production is associated with chronic kidney disease. In the present study, we investigated the impact of gender, CsA dose and renal NO synthase (NOS) on CAN. 2. Kidneys from male and female F344 rats were transplanted into same-sex Lewis allograft or F344 isograft recipients and recipient rats were treated with 1.5 or 3 mg/kg per day CsA for 10 days. Grafts were removed at 22 weeks post-transplantation. Normal two-kidney F344 rats were investigated as age-matched controls. 3. Low-dose CsA was associated with accelerated CAN in female rats compared with male rats; however, with high-dose CsA, allograft females had similar pathology/function to allograft males. Isograft females (similar to isograft males) had no graft failure and only slightly, albeit significantly, greater injury than age-matched controls. Isograft females had higher renal cortical neuronal (n) NOS but lower medullary endothelial (e) NOS than isograft males. There was no difference in renal eNOS and nNOS between allograft groups. 4. In conclusion, 1.5 mg/kg per day CsA is not sufficient to prevent early graft loss in females. When the dose of CsA is doubled, allograft females and males have similar post-transplant survival. Renal NOS expression was unremarkable in any transplant group.     

联苯双酯对肾移植受者环孢素A全血浓度的影响及肝毒性的防护作用

目的 :研究肾移植受者应用联苯双酯 (bifen date ,BFD)对环孢素A(cyclosporinA ,CsA)全血浓度的影响及肝毒性的防护作用。方法 :2 8例患者 (合用组 )合用CsA与BFD ,30例患者 (对照组 )单服CsA ,以CsA全血浓度及肝功能作为临床评价指标。结果 :BFD能有效降低肾移植受者异常升高的ALT和AST ,合用BFD后CsA全血浓度与合用前比较降幅达 17.7% ,与对照组比较亦有显著性降低 (P <0 .0 1) ,停用BFD后CsA全血浓度明显升高 ,增幅达36 .3%。结论 :BFD能防护肾移植受者CsA肝毒性并能明显降低CsA血浓度。     

Effect of oral posaconazole on the pharmacokinetics of cyclosporine and tacrolimus

STUDY OBJECTIVE: To analyze the pharmacokinetic properties of the immunosuppressants cyclosporine and tacrolimus when either is coadministered with oral posaconazole. DESIGN: Two single-center, open-label pharmacokinetic studies of cyclosporine in a multiple-dose design and of tacrolimus in a one-sequence, crossover, single- and multiple-dose design. SETTING: One clinical investigative center in the United States and one in the United Kingdom. SUBJECTS: Four adult heart transplant recipients in the cyclosporine study and 36 healthy adult volunteers in the tacrolimus study. INTERVENTIONS: In the cyclosporine study, patients who took an established cyclosporine dose 3 times/day for 6 weeks or longer were given posaconazole 200 mg/day for 10 days. In the tacrolimus study, subjects received tacrolimus 0.05 mg/kg/day on days 1 and 14 and posaconazole 400 mg twice/day on days 7-14. MEASUREMENTS AND MAIN RESULTS: In the cyclosporine study, blood samples were collected on day 1 to determine cyclosporine pharmacokinetics and on day 10 to measure the pharmacokinetics of cyclosporine and posaconazole. Coadministration of posaconazole increased cyclosporine exposure and necessitated dosage reductions of 14-29% for cyclosporine in three subjects. In the tacrolimus study, blood samples were collected on days 12-14 to assess posaconazole pharmacokinetics and on days 1 and 14 for as long 72 hours after dosing to evaluate tacrolimus pharmacokinetics. Posaconazole increased the maximum blood concentration and the area under the concentration-time curve for tacrolimus by 121% and 358%, respectively, on day 14 compared with day 1 (both p=0.001). In both studies, posaconazole pharmacokinetics were unaffected. CONCLUSION: These findings suggest that the dosage of cyclosporine or tacrolimus should be reduced when posaconazole therapy is started and that plasma levels of the immunosuppressant should be monitored during and at the discontinuation of posaconazole therapy so that dosages are adjusted accordingly. This recommendation is consistent with current standard of care for patients receiving cyclosporine or tacrolimus with concomitant azole antifungal therapy.