临床药师对1例肾移植术后排斥患者的药学服务

目的 以1例出现术后排斥的肾移植患者为例,探讨临床药师在肾移植受者术后排斥治疗中的药学监护要点。方法 临床药师参与1例肾移植术后发生排斥反应患者的治疗,从调整优化用药方案、关注药物的疗效及不良反应、注意药物的相互作用、以及提供患者用药教育等方面,实施全方位的药学监护。结果 患者肾功能有所好转,治疗期间临床药师提供全方位临床药学服务,完善及提高了临床药物治疗实施。结论 临床药师参与肾移植受者术后治疗团队,为患者制订个体化的药学监护,进行临床药学服务,可保证患者用药安全、有效。     

肾移植病人应用霉酚酸酯与硫唑嘌呤的临床疗效比较

目的：比较霉酚酸酯（MMF）、硫唑嘌呤（Aza）在肾移植病人中的临床效果。方法：肾移植术后服用霉酚酸酯、硫唑嘌呤患者各28例，均采用同服环孢菌素和泼尼松三联用药方案，每月常规监测环孢菌素A（CsA）全血浓度、血常规、肾功能、肝功能、尿常规。结果：MMF组的CsA用量及其血药浓度显著低于Aza组（P〈0．05），MMF组患者血肌酐（Cr）值也显著低于Aza组（P〈0．05），同时MMF组对急慢性排斥反应效果较Aza组好，药物性肝损害发生率低于Aza组。结论：MMF较Aza不良反应小，减少或避免肝、肾功肾功能损害的发生机会，使肾移植的成功率明显提高。     

肾移植术后多尿期“量化模式”补液的探讨

目的探讨并完善肾移植术后患者多尿期的补液模式。方法对63例肾移植术后患者多尿期护理资料进行回顾性分析,观察＂量化模式＂补液对控制肾移植患者术后转归的影响。结果 63例患者,3例发生超急性排斥反应,2例发生急性排斥反应,1例发生移植肾功能恢复延迟,57例患者肾功能恢复顺利,多尿期未发生水、电解质、酸碱平衡紊乱,与同期28例传统补液方案的病例相比,t1/2（Scr）明显缩短。结论采用＂量化模式＂补液,可减少肾移植患者术后水、电解质和酸碱平衡紊乱等并发症,促进移植肾功能的恢复。     

氨苄青霉素与甲硝唑对剖宫产产妇术后预防产褥感染的临床疗效评价

目的:评价氨苄青霉素与甲硝唑对剖宫产产妇术后预防产褥感染的临床疗效。方法:选取2016年3月—2017年5月期间收治的剖宫产产妇100例资料,采用随机双盲原则将其分观察组50例和对照组50例;对照组产妇术后给予氨苄青霉素预防产褥感染;观察组患者术后则给予氨苄青霉素与甲硝唑联用预防产褥感染;比较两组产妇产后产褥感染的发生率和有效率差异。结果:观察组产妇用药后体温复常时间和白细胞计数优于对照组(P<0.05);观察组产妇术后产褥感染的发生率低于对照组(P<0.05)。结论:采用氨苄青霉素与甲硝唑联用可有效预防剖宫产产妇术后产褥感染的发生,促进了产妇感染症状的复常。     

环孢菌素能引起肾小球滤过率和脲分泌改变吗

<正> 在2组肾移植病人(移植肾功能正常)中进行了一项研究,以阐明环孢菌素对肾移植病人(中度血管内容量减液效应后)肾功能的影响.     

热淋清颗粒治疗肾移植术后泌尿系感染20例临床观察

本研究从2002年5月至2006年2月对20例肾移植术后泌尿系感染的患给予热淋清颗粒治疗，并与同期肾移植术后20例泌尿系感染的患采用复方磺胺甲嘿唑（抗菌优）或诺氟沙星（氟哌酸）治疗进行了对照，现报告如下。     

肾移植术后10年以上患者PRA与肾功能关系的研究

肾移植患者移植肾长期存活是肾移植患者和临床医生非常殷切的希望,但在临床方面多关注于除手术因素外、还有急性排斥、慢性排斥、术后感染、药物中毒和术后肿瘤的发生等多种因素,目前肾移植对上述问题大多都有相应的措施进行治疗。而对于群体反应性抗体(PRA)对移植肾长期存活以及PRA对移植肾功能的影响国内则研究较少,因此本文仅对肾移植术后存活10年以上的患者进行PRA和肾功能进行研究,报     

3例肾移植术后妊娠分娩患者的护理

随着肾移植技术和围生医学的发展,肾移植术后患者肾功能改善及生殖机能恢复,育龄妇女术后妊娠的梦想已成为现实。肾移植患者术后妊娠具有高度的危险性,妊娠导致肾功能的恶化及排斥反应和感染率的增加。所以加强对肾移植术后妊娠及产后的监护,使患者安全渡过围生期,保证母婴的安全是护理工作的重要内容。现将3例肾移植术后     

抗生素在预防胃肠手术切口感染中的应用

目的探讨抗生素在预防胃肠手术切口感染中的应用效果。方法分析本院普外科收治的胃肠手术患者60例临床资料,根据抗生素种类不同进行分组,氨苄青霉素组30例和头孢呋辛组30例。结果氨苄青霉素组和头孢呋辛组术后第2天、术后第4天白细胞数、中性粒细胞数、血红蛋白数均无明显差异,P〉0.05无统计学意义。结论氨苄青霉素和头孢呋辛在预防胃肠手术切口感染中的应用效果明显,值得临床借鉴应用。     

喹诺酮类注射液与常用药物配伍的稳定性

随着第三代喹诺酮类抗菌药物的广泛使用,临床上将喹诺酮注射液与输液及其它常用药物的配伍使用日渐增多,现就有关文献综述如下：１诺氟沙星诺氟沙星葡萄糖注射液与氨苄青霉素钠配伍后即出现白色沉淀并悬浮于溶液中,与苯唑青霉素钠混合５ｍｉｎ后产生黄色沉淀,均属配伍...     

头孢呋辛对肾移植患者肾功能和环孢素血浓度的影响

采用FPIA法测定环孢素血药浓度,在32例肾移植术后患者中进行合用头孢呋辛对肾功能及环孢素血药浓度影响的研究.在合用头孢呋辛前、合用7d后、停药后d7测定患者的血清肌酐、尿素氮和环孢素全血谷值药物浓度.结果患者合并用药前、后的血清肌酐、尿素氮、环孢素浓度经统计学检验无显著性差异(P>0.05).表明头孢呋辛与环孢素合用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.     

Therapeutic drug monitoring of cyclosporine-lipoprotein levels

Cyclosporine therapy is complicated by nephrotoxicity that is not predicted by drug levels. In this study serial trough blood samples were obtained from 11 allogeneic marrow transplant recipients after initiation of intravenous cyclosporine 2 mg/kg every 12 hours for a period extending 4 weeks after transplantation. Renal dysfunction, assessed by an increase in serum creatinine levels to twice baseline values or when greater than 175 mumol/L, was found in four patients. No associations between renal dysfunction and cyclosporine levels in whole blood, total plasma, or lipoprotein fractions were found. The ratios of maximum and mean high-density low-density lipoprotein cyclosporine concentrations were greatest in patients with renal dysfunction (p less than 0.001). The data suggest therapeutic drug monitoring of cyclosporine in various biologic fluids does not predict onset of drug-associated renal dysfunction. However, the relative role of high-density to low-density lipoprotein transport of cyclosporine may provide an index of renal functional changes associated with the agent.     

3种 头孢菌素对肾功能及环孢素血浓度的影响

５１例肾移植术后患者中随机分组，考查３种新头孢菌素分别与环孢素合并使用时对肾功能及环孢素全血药浓浓度的影响，在合并用头孢菌素前，合并用药７ｄ，停药后７ｄ测定患者的血清肌酐、尿素氮和环孢素全血药物浓度。     

肾移植术后高脂血症的影响因素研究

目的：研究肾移患者植术后高脂血症的影响因素。方法：回顾分析826例肾移植患者中出现高脂血症的267例患者,调查术后时间、环孢素（CsA）全血浓度对患者移植术后血脂影响,及高血脂对患者肝、肾功能和血糖的影响。结果：肾移植术后0～3个月、4～6个月、7—12个月、1—2年高脂血症发生率分别为6．8％、7．0％、7．6％、10．9％,患者首次血脂异常时的总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）水平与CsA全血浓度呈相关趋势。肾移植患者出现高血脂时,其血肌酐（SCr）和血糖（Glu）也明显升高,服药降低血脂后,SCr和Glu明显下降至血脂异常前水平（P〈0．05）,而未服用调脂药仅控制饮食的患者,首次血脂异常后3个月的Glu和SCr水平继续升高,显著高于首次血脂异常时的水平（P〈0．05）。结论：CsA对肾移植患者术后血脂的影响呈一定的浓度依赖性;术后1年内是肾移植受者高血脂症高发期。高血脂可明显影响移植肾功能,同时使患者血糖升高,应密切监测血脂变化．及时降脂治疗。     

Two-hour cyclosporine concentration determination: an appropriate tool to monitor neoral therapy?

Cyclosporine is a critical dose drug for which individualisation by therapeutic drug monitoring is indisputable. Current evidence suggests that a single concentration (C2) taken two hours after cyclosporine administration with the microemulsion formulation better predicts exposure and events than the trough concentration (C(0)), which is routinely used for adjusting the dosage of this drug. Studies have shown that the greatest calcineurin inhibition and the maximum inhibition of IL-2 production occur in the first 1 to 2 hours after dosing. These findings support the concept that the C2 level better reflects immunosuppressive efficacy than the trough concentration. Preliminary data from an outcome study in liver transplant recipients have shown that the incidence of biopsy proven moderate to severe acute rejection was significantly lower in patients managed by C2 monitoring compared with those monitored by C(0). The critical importance of achieving adequate cyclosporine exposure during the first 3 to 5 posttransplant days to prevent acute rejection has been documented in prospective studies with de novo renal and liver transplant recipients. Conversion of maintenance liver and heart transplant patients to C2 monitoring resulted in an amelioration of renal function. Time-dependent target values have been proposed for liver and renal transplant recipients. These require further prospective validation. For routine monitoring of C2 levels on-site validated dilution guidelines are necessary for most of the available immunoassays. C2 monitoring necessitates further organizational requirements which may be judged differently between transplant centers. In particular during the early posttransplant period C2 monitoring is a promising new option to make immunosuppressive therapy with the microemulsion formulation of cyclosporine safer and more efficient.     

Review of the proliferation inhibitor everolimus

Everolimus (Certican^?) is being developed for prevention of acute and chronic rejection of solid organ transplants. A novel proliferation inhibitor, everolimus synergies with cyclosporine to prevent and reverse acute rejection in preclinical models of kidney, heart or lung transplantation. The manifestations of chronic rejection that may contribute to graft loss are also inhibited by everolimus in preclinical models. Although everolimus is metabolised by the cytochrome P450 CYP3A isoenzyme, coadministration with cyclosporine does not alter the pharmacokinetics of cyclosporine, but cyclosporine coadministration increases exposure to everolimus. Everolimus interacts with inhibitors and inducers of this system; its clearance is reduced in patients with hepatic impairment. In an immunosuppressive regimen with cyclosporine microemulsion formulation and corticosteroids, transplant recipients treated with everolimus show low rates of acute rejection and, in one heart and one renal trial, lower rates of cytomegalovirus infection. Acute rejection rates are lower than those seen with azathioprine in cardiac transplant recipients and similar to those seen with mycophenolate mofetil in renal transplant recipients. Low rates of acute rejection are maintained when everolimus is given as part of a quadruple immunosuppressive regimen with low-dose cyclosporine in renal transplant recipients, with the added benefit of better renal function compared with full-dose cyclosporine. Use of C₂ monitoring to optimise cyclosporine exposure and enhance efficacy and safety of everolimus is planned in future studies. Hypertriglyceridaemia and hypercholesterolaemia have been associated with everolimus, but these effects are not dose-limiting. There is no clear upper therapeutic limit of everolimus. However, thrombocytopenia occurs at a rate of 17% at everolimus trough serum concentrations above 7.8 ng/ml in renal transplant recipients. There are limited safety data available in patients with trough concentrations > 12 ng/ml. Studies suggest everolimus targets primary causes of chronic rejection by reducing acute rejection, allowing for cyclosporine dose reduction (which may lead to improved renal function relative to full-dose cyclosporine) and by reducing cytomegalovirus infection and inhibiting vascular remodelling.     

Evaluation of the pharmacokinetic interaction between fluvastatin XL and cyclosporine in renal transplant recipients

OBJECTIVE: To assess the pharmacokinetic interaction between cyclosporine and extended-release fluvastatin (fluvastatin XL), 80 mg for 7 days, in stable renal transplant recipients. METHODS: This was a single-center, open-label study. 17 renal transplant recipients received their standard cyclosporine therapy (Days 1 - 9) plus a once-daily single oral dose of fluvastatin XL, 80 mg (Days 2 - 8). Blood samples were collected and cyclosporine (whole blood) and fluvastatin (plasma) concentrations determined by radioimmunoassay and HPLC fluorescence detection, respectively. Pharmacokinetic parameters were calculated using non-compartment analysis and fluvastatin results were compared with historical controls. RESULTS: Treatment with fluvastatin XL, 80 mg for 7 days, had no significant effect on either the AUC0-12 (3,644 ng x h/ml in the absence of fluvastatin vs. 3,534 ng x h/ml in the presence of fluvastatin) or the Cmax of cyclosporine (983 ng/ml in the absence of fluvastatin vs. 945 ng/ml in the presence of fluvastatin). Co-administration of fluvastatin XL also had no effect on the tmax, t1/2 or apparent clearance (CL/F) of cyclosporine in renal transplant patients. The AUC and Cmax for fluvastatin XL in the presence of cyclosporine (AUC0-24 1,192 ng. x h/ml, Cmax 271 ng/ml) were approximately 2-fold higher compared with historical data for fluvastatin XL alone in healthy volunteers (AUC0-24 630 ng x h/ml, Cmax 102 ng/ml) but lower than the historical data for fluvastatin IR, 40 mg b.i.d. alone in healthy volunteers (AUC0-24 1,340 ng x h/ml, Cmax 443 ng/ml). Tmax, t1/2 and trough levels of fluvastatin in the presence of cyclosporine were also similar to the historical controls. Concomitant administration of cyclosporine and fluvastatin XL was well tolerated by renal transplant recipients. CONCLUSIONS: Fluvastatin XL, 80 mg, and cyclosporine do not show clinically relevant pharmacokinetic interactions.     

Review of the proliferation inhibitor everolimus

Everolimus (Certican) is being developed for prevention of acute and chronic rejection of solid organ transplants. A novel proliferation inhibitor, everolimus synergies with cyclosporine to prevent and reverse acute rejection in preclinical models of kidney, heart or lung transplantation. The manifestations of chronic rejection that may contribute to graft loss are also inhibited by everolimus in preclinical models. Although everolimus is metabolised by the cytochrome P450 CYP3A isoenzyme, coadministration with cyclosporine does not alter the pharmacokinetics of cyclosporine, but cyclosporine coadministration increases exposure to everolimus. Everolimus interacts with inhibitors and inducers of this system; its clearance is reduced in patients with hepatic impairment. In an immunosuppressive regimen with cyclosporine microemulsion formulation and corticosteroids, transplant recipients treated with everolimus show low rates of acute rejection and, in one heart and one renal trial, lower rates of cytomegalovirus infection. Acute rejection rates are lower than those seen with azathioprine in cardiac transplant recipients and similar to those seen with mycophenolate mofetil in renal transplant recipients. Low rates of acute rejection are maintained when everolimus is given as part of a quadruple immunosuppressive regimen with low-dose cyclosporine in renal transplant recipients, with the added benefit of better renal function compared with full-dose cyclosporine. Use of C(2) monitoring to optimise cyclosporine exposure and enhance efficacy and safety of everolimus is planned in future studies. Hypertriglyceridaemia and hypercholesterolaemia have been associated with everolimus, but these effects are not dose-limiting. There is no clear upper therapeutic limit of everolimus. However, thrombocytopenia occurs at a rate of 17% at everolimus trough serum concentrations above 7.8 ng/ml in renal transplant recipients. There are limited safety data available in patients with trough concentrations > 12 ng/ml. Studies suggest everolimus targets primary causes of chronic rejection by reducing acute rejection, allowing for cyclosporine dose reduction (which may lead to improved renal function relative to full-dose cyclosporine) and by reducing cytomegalovirus infection and inhibiting vascular remodelling.     

环孢素浓度对肾移植术后患者血脂的影响

目的 :观察环孢素浓度对肾移植术后患者血胆固醇及甘油三酯水平的影响。方法 :对50名肾移植术后患者 ,在术后1、3、6个月同时测定环孢素、胆固醇及甘油三酯水平 ,并将患者按不同时间及环孢素谷浓度进行分组。用SPSS8 0独立样本t检验进行统计学处理。结果 :肾移植术后第6个月与第1个月比较 ,胆固醇、甘油三酯水平有显著性差异 (P<0 05及P<0 01) ;在肾移植术后第6个月 ,环孢素谷水平大于或小于400μg/L ,胆固醇有显著性差异 (P<0 05)。结论 :服用环孢素尤其是高血药浓度可能是胆固醇、甘油三酯升高的原因之一     

Possible Role of the Intestinal P-450 Enzyme System in a Cyclosporine-Clarithromycin Interaction

Clarithromycin is a macrolide antibiotic similar in structure to erythromycin, but suggested to have fewer drug interactions. Although a pharmacokinetic interaction between clarithromycin and cyclosporine was recently reported, its magnitude and mechanism have not been explored. A 43-year-old renal transplant recipient receiving cyclosporine was treated with clarithromycin because of pneumonia. A cyclosporine pharmacokinetic study was performed 8 days after the initiation of the clarithromycin and 14 days after stopping the drug. Clarithromycin coadministration caused an approximately 2-fold increase in the area under the whole blood concentration versus time curve of cyclosporine. The oral clearance of cyclosporine was halved by clarithromycin, but the terminal elimination rate constant decreased only 15% and mean residence time 20%. These observations suggest that clarithromycin inhibits not only the hepatic metabolism but also the intestinal metabolism of cyclosporine. Caution is advised when administering the two drugs concurrently, and additional studies are necessary to elucidate the mechanism of this interaction.