肾移植术后受者环孢素的血药浓度监测

目的 观察环孢素血药浓度与肾移植效果间关系。方法 对97例接受同种异体肾脏移植术受术后8周内206例次环孢素血药浓度监测结果进行回顾性分析，按照受术后的临床表现、生化指标将其分为术后正常组、急性排斥组、急性毒性组，采用荧光偏振免疫测定法，以单克隆抗体试剂测定环孢素血药浓度。结果 术后正常组62例移植肾功能良好，环孢素的给药剂量为5．2±1.9mg/kg·d，171例次环孢素血药浓度的平均值为309．85±131．69μg/L;术后急性排斥组26例，距发生排斥反应最近一次的环孢素血药浓度平均为165．80±123．13μg/L ,环孢素的给药剂量为4．8±1．6mg/kg·d；术后急性毒性组9例，距发生毒性反应最近一次的环孢素血药浓度平均为556．51±102．50μg/L，环孢素的给药剂量为6．2±1．0mg/kg·d。三组之间环孢素的给药剂量无显性差异（P＞0．05），但环孢素血药浓度却相差很大，两两之间有显性差异（正常组与排斥组P＜0．05；正常组与毒性组P＜0．05；排斥组与毒性组（P＜0．01）。结论 环孢素浓度较低时，出现排斥反应的可能性较大；而环孢素浓度较高时，发生毒性反应的机会较多。     

肾移植受者环孢素血药浓度监测频度及其临床意义

目的:研究肾移植术后患者环抱素(CsA)血药浓度监测频度的临床意义。方法:对24例肾移植术后患者296次CsA血药浓度监测进行回顾性分析,分2组:规律组15例201次规律性监测;非规律组9例95次因各种原因不能定期监测。比较2组CsA血药浓度统计学变异系数(CV)的差异及排斥反应组与非排斥反应组CsA血药浓度CV的差异。结果:规律组CsA血药浓度CV小于非规律组(P<0.05);非排斥组CsA血药浓度CV小于排斥组(P<0.05)。结论:规律性CsA血药浓度比非规律性监测平稳;排斥反应的发生率与CsA血药浓度的CV呈正相关。     

肾移植术后CsA血药浓度监测及其临床意义

环孢素A(cyclosporine,CsA)有较强的免疫抑制作用,临床上广泛用于防止肝、肾、骨髓等器官移植的免疫排斥反应和治疗自身免疫性疾病。由于该药的生物利用度和药代动力学个体差异大,具有较强的肝、肾毒性,所以,应用时要密切监测其血药浓度,及时地调整剂量以防止发生肾中毒或排斥反应。本文收集了2003年66例肾移植术后患者330例次CsA血药浓度数据加以分析,供临床用药参考。1对象和方法1.1对象:肾移植受者手术后来我实验室监测CsA血药浓度的患者,年龄20～69岁,共监测330例次,男222例次,女108例次。1例CsA血药浓度很高,经查,上午于服药后40mi…     

肾移植患者血中环孢素A监测及最佳浓度探讨

对２３例肾移植患者进行了２４３次血药浓度监测．并对术后不同时期环孢素Ａ最佳治疗浓度进行了探讨。结果表明肾移植术３个月后血中环孢素Ａ控制在３５０ｎｇ／ｍｌ为宜。     

肾移植术后环孢素A血药浓度监测与临床疗效关系

目的:研究肾移植(RT)术后环孢素A(CsA)浓度与临床疗效之间的关系。方法:将RT患者分成3组:正常组、中毒组、排异组。应用荧光偏振免疫(FPIA)法,对921例次RT术后患者进行常规CsA血药浓度监测,同时观察疗效。结果:平均血浓度正常组为256.10±47.52ng/ml;排异组为142.25±44.71ng/ml;中毒组为432.96±107.99ng/ml。正常组分别与中毒组、排异组之间血药浓度的显著性差异(P<0.001)。结论:CsA血药浓度监测可以指导临床合理用药,避免或减少不良反应。     

肾移植术后环孢素A血药浓度监测及临床意义

目的 探讨肾移植术后环孢素A血药浓度监测在临床中应用价值及意义.方法 对26例肾移植术后患者采用三联免疫抑制用药方案,并对其进行不同时间的CsA血药浓度监测,同时对药物的不良反应进行临床总结.结果 肾移植术后不同时间的平均CsA血药浓度监测示:<1月为(341±53.7)ng/ml,1月为(309±49.4)ng/ml,3月为(286±46.1)ng/ml,6月为(237±41.5)ng/ml,1年为(218±39.3)ng/ml,>1年为(164±37.8)ng/ml.26例肾移植术后患者,出现急性排斥反应5例占19.23%.结论 肾移植术后实施CsA用药个体化方案,监测CsA血药浓度,及时调整药物剂量,是指导临床医师调整给药方案重要依据.     

68例肾移植受者环孢素血药浓度监测

目的:分析环孢素血药浓度与剂量、疗效的关系。方法:以高效液相色谱法对68例肾移植受者进行556次环孢素血药浓度监测。结果:肾移植术后不同时期环孢素全血谷浓度分别为289.3±126.0(1个月),229.2±101.6(2个月),199.1±108.7(3个月),144.9±53.5(4～12个月),135.6±51.9ng·ml~(-1)(>12个月),500例次肝肾功能正常,占89.9％,53例次不正常,占9.5％,3例次出现慢性排斥,经应用激素冲击疗法和增加环孢素用量得以纠正。结论:环孢素血药浓度监测具有重要的临床意义。     

肾移植术后患者环孢素A血药浓度监测结果分析

目的分析肾移植(RT)术后患者环孢素A(CsA)血药浓度监测情况,指导临床合理用药。方法采用高效液相色谱法(HPLC)对2007年8月至2009年12月来中国人民解放军第201医院的72例肾移植术后患者357例次CsA血药浓度进行监测,并对其CsA谷浓度(C0)、术后时间、性别进行回顾性分析。结果在72例肾移植术后患者357例次CsA血药浓度监测中,88.8%达到有效血药浓度(100～400μg/L),6.4%低于有效血药浓度(<100μg/L),4.8%高于有效血药浓度(>400μg/L)。CsA血药浓度和服药剂量随术后时间的延长呈现下降趋势,且个体差异较大。术后24个月,男女两组血药浓度具有显著性差异(P<0.05)。结论由于环孢素A不良反应大,治疗窗范围窄,因此应定期监测CsA血药浓度并及时调整给药方案,对于提高肾移植患者的长期存活率,降低其毒性和不良反应具有重要的临床意义。     

肾移植患者环孢素A血药浓度监测及结果分析

目的 了解肾移植患者环孢素A(CsA)血药浓度变化情况,提高患者用药安全性.方法 收集2007年1月-2010年1月我院197例肾移植受者术后CsA血药浓度监测资料进行回顾性分析.结果 在197例肾移植患者906例次CsA血药浓度监测中,达到有效血药浓度(100～400μg/L)569例次(62.8%),平均浓度为(175.33±65 97)μg/L;低于有效血药浓度(＜100μg/L)145例次(16.0%),平均浓度为(72.99±19.22)μg/L;高于有效血药浓度(＞400μg/L)192例次(21.2%),平均浓度为(808.25±279.78)μg/L.结论根据患者CsA血药浓度监测结果,制定个体化给药方案,可避免毒性反应和排异反应的发生,提高患者用药安全性,减少不良反应的发生.     

肾移植术后环孢素C2治疗窗的临床研究

目的 初步研究肾移植术后环孢素C2的治疗窗范围。方法 用特异性荧光偏振免疫法(FPIA)测定58例肾移植受者C2浓度667人次,并按术后不同时间和临床诊断分组比较。结果 肾移植术后应用三联免疫抑制治疗中,理想的C2治疗窗浓度范围为:术后第1个月内(1 374.51±271.25)ng·mL-1,术后第2个月内(1 328.59±231.05)ng·mL-1,术后第3月内(1 117.05±182.46)ng·mL-1,4个月以上(964.07±136.52)ng·mL-1。结论 该浓度范围免疫抑制效果满意,排斥反应与药物中毒的发生率相对较少,可作为国人肾移植受者C2治疗窗浓度范围的参考。     

Relationships between thiopurine S-methyltransferase polymorphism and azathioprine-related adverse drug reactions in Chinese renal transplant recipients

Objective  To systematically investigate the relationships between thiopurine S-methyltransferase (TPMT) polymorphisms and azathioprine-related adverse drug reactions in patients with kidney transplantation. Methods  Erythrocyte TPMT activity of 150 patients with kidney transplantation and AZA therapy was determined by HPLC. The frequency of four common TPMT mutant alleles, TPMT*2, *3A, *3B, and *3C was determined by allele-specific PCR and PCR-restriction fragment length polymorphism (PCR-RFLP) analysis. Results  Thirty cases (20%) had stopped azathioprine medication or were on reduced dose due to azathioprine-related side effects. The TPMT activity range of cases who never experienced side effects was 16.63-68.25 U, the mean of the controls was 38.43 ± 11.59 U. The mean value of 12 cases with hematotoxicity was 23.50 ± 10.33 U, much lower than the control mean (P < 0.05). No significant difference between the mean value of 18 cases with hepatotoxicity and the control mean (P > 0.05) was seen. No case with TPMT deficiency was found in all patients studied, and TPMT*2, *3A, and *3B were not detected in any of them. TPMT*3C heterozygous alleles were found in 4.7% (seven cases) of these patients, all seven cases had intermediate TPMT activity, and the mean was 16.75 ± 2.09 U, much lower than other TPMT wild-type patients (P < 0.05). In the seven TPMT*3C patients, four cases experienced side effects (hematotoxicity, n = 2; hepatotoxicity, n = 2). Conclusions  This study demonstrates that TPMT activity is reduced in patients with TPMT*3C mutation. AZA-induced hematotoxicity is related to the reduced TPMT activity.     

Aerosol drug delivery in lung transplant recipients

Background: Inhaled drug delivery after lung transplantation provides a unique opportunity for direct treatment of a solid organ transplant. At present, no inhaled therapies are approved for this population though several have received some development. Primary potential applications include inhaled immunosuppressive and anti-infective drugs. Objectives: The objective of this article is to review potential applications of inhaled medications for lung transplant recipients, the techniques used to develop inhaled drugs and the challenges of aerosol delivery in this specific population. Methods: The results of relevant studies are reviewed and two developmental examples are presented. Results/conclusions: Inhaled medications may provide significant advantages for lung transplant recipients. Past studies with inhaled cyclosporine and amphotericin-B provide useful guidance for clinical development of new preparations.     

A comparison of the pharmacokinetics of tacrolimus and microemulsified cyclosporin in paediatric renal transplant recipients

Objective Our objective was to identify common factors that determine the dose of tacrolimus and microemulsified cyclosporin in paediatric renal transplant recipients.Methods The concentration profiles of tacrolimus and cyclosporin in blood were determined in 68 children who had received a renal transplant. To avoid disruption of therapy, measurements were made at 2-h intervals over an 8-h period during normal dosing regimens. Direct comparisons of the two drugs were made in 14 of the subjects who were switched from cyclosporin to tacrolimus.Results The ratio of peak to trough levels for tacrolimus was approximately twofold compared with over threefold for cyclosporin. Area under the curve (AUC) for tacrolimus remained relatively constant in each 2-h period of the dosage interval compared with the AUC for cyclosporin, which varied by over twofold in the same time period. In the 14 subjects who received both drugs, there was a poor correlation between C₂/C₀, C₂, t_1/2 and AUC for tacrolimus and cyclosporin in the same individual. In a multivariate analysis, there were no significant associations for tacrolimus concentrations, AUC or C₂/C₀ with age, gender, calcium-channel blocker, quinolone or statin. For cyclosporin, there was some association for AUC with gender and quinolone use and a weak association with calcium-channel blocker or statin use.Conclusions Tacrolimus and microemulsified cyclosporin display a wide intra- and inter-individual variation in pharmacokinetic properties in young subjects. In the case of absorption represented by the peak-trough ratios, the values for tacrolimus are significantly less than those obtained with cyclosporin. The pharmacokinetic parameters obtained for one of these agents is not predictive for the behaviour of the other in young renal transplant recipients.     

肾移植术后吗替麦考酚酯替换硫唑嘌呤的临床分析

目的 :观察肾移植后吗替麦考酚酯 (MMF)替换硫唑嘌呤 (Aza)的安全性及其临床效果。方法 :回顾分析16例由Aza转换为MMF患者的临床资料。4例因肝功能损害而改用MMF,7例肾功能损害 ,5例应患者要求而换用MMF。结果 :4例肝功能损害者肝功能均恢复正常 ,7例肾功能损害者2例逆转 ,4例肌酐 (SCr)下降但未能恢复正常 ,1例继续恶化恢复血液透析。2例不良反应包括原有贫血明显加重 ,1例腹泻。结论 :Aza可以安全替换为MMF。因环孢素 (CsA)加Aza引起肝功能损害者 ,换用MMF ,减少CsA用量 ,肝功能可望恢复。MMF对部分慢性排斥反应可能有效     

肝移植受者他克莫司治疗窗浓度的初步探讨

目的探讨肝移植受者他克莫司治疗窗浓度参考范围。方法采用化学发光微粒子免疫法(CMIA)监测他克莫司全血谷浓度(C0),结合受者的临床表现及生化指标,对74例肝移植受者的305例次监测结果进行分析。结果肝移植术后前3个月他克莫司C0为(7.0±3.6)ng/ml,3个月后为(5.5±2.3)ng/ml。术后发生急性排斥反应4例次,肝、肾毒性54例次。结论建议将实验室他克莫司治疗窗范围进行调整:肝移植术后前3个月为7～15ng/ml,3个月后为5～10ng/ml,以保证免疫抑制效果,减少排斥反应和肝、肾毒性。     

肝移植受者他克莫司治疗窗浓度的初步确定

目的寻求适合国人肝移植受者他克莫司理想治疗窗浓度范围.方法应用微粒子酶免分析法测定69例肝移植患者口服他克莫司后12 h的血药谷浓度,并观察排斥反应的发生及药物的不良反应.结果他克莫司的血药浓度,术后第1个月为(13.1±2.0)μg*L-1,第2,3个月为(9.2±1.7)μg*L-1,3个月后为(6.3±1.2)μg*L-1,比较各时期全血他克莫司谷浓度,差异均有极显著性(P＜0.01).术后发生排斥反应64例次,不良反应73例次.结论他克莫司治疗窗浓度范围术后第1个月为10～15 μg*L-1,第2、3个月为7.0～11 μg*L-1,3个月后为5.0～8.0 μg*L-1维持,此浓度范围既能达到满意的免疫抑制效果,又能减少他克莫司的不良反应.     

肾移植术后受者环孢素的血药浓度监测

目的 观察环孢素血药浓度与肾移植效果间关系。方法 对９７例接受同种异体肾脏移植术受者术后８周内２０６例次环孢素血药浓度监测结果进行回顾性分析，按照受者术后的临床表现、生化指标将其分为术后正常组、急性排斥组、急性毒性组，采用荧光偏振免疫测定法，以单克隆抗体试剂测定环孢素血药浓度。结果 术后正常组６２例移植肾功能良好，环孢素的给药剂量为５２±１．９ ｍｇ／ｋｇ·ｄ，１７１例次环孢素血药浓度的平均值为３０９．８５±１３１．６９μｇ／Ｌ；术后急性排斥组 ２６例，距发生排斥反应最近一次的环孢素血药浓度平均为１６５．８０±１２３．１３μｇ／Ｌ，环孢素的给药剂量为 ４．８±１．６ｍｇ／ｋｇ·ｄ；术后急性毒性组９例，距发生毒性反应最近一次的环孢素血药浓度平均为５５６．５１±１０２．５０μｇ／Ｌ，环孢素的给药剂量为６．２±１．０ｍｇ／ｋｇ·ｄ。三组之间环孢素的给药剂量无显著性差异（Ｐ＞０．０５），但环孢素血药浓度却相差很大，两两之间有显著性差异（正常组与排斥组 Ｐ＜ ０．０５；正常组与毒性组Ｐ＜ ０．０５；排斥组与毒性组Ｐ＜ ０．０１）。结论 环孢素浓度较低时，出现排斥反应的可能性较大；而环孢素浓度较高时，发生毒性反应的机会较多。     

移植肾功能延迟恢复患者早期应用前列地尔临床观察

目的 评估前列地尔在肾移植术后移植肾功能延迟恢复(DGF)患者早期应用对促进移植肾功能恢复的效果.方法 回顾性分析肾移植术后发生移植肾功能延迟恢复应用前列地尔患者16例,与同期未使用前列地尔的DGF患者14例进行比较,比较两组间术后尿量、血肌酐(SCr)、移植肾血流阻力指数、急性排斥反应的发生率及1年人/肾生存率.结果 应用前列地尔的患者术后尿量明显大于对照组(P ＜0.05);SCr浓度、移植肾血流阻力指数均明显低于对照组(均P ＜0.05);两组急性排斥反应发生率差异无统计学意义(P＞0.05).结论 肾移植受者术后DGF患者早期应用前列地尔有利于促进移植肾功能的恢复.