他克莫司治疗儿童肾小球疾病血药浓度监测及临床疗效评价

目的 通过研究儿童肾小球疾病治疗药物他克莫司血药浓度监测及用药情况,评价他克莫司治疗肾小球疾病的疗效及不良反应.方法 选取2019年4月至2021年4月服用他克莫司治疗肾小球疾病的患儿,记录他克莫司血药谷浓度,临床病理生理指标,观察不良反应,评估临床疗效等.结果 89例患儿监测他克莫司血药谷浓度201次,达标率为48....     

他克莫司的临床应用评价

目的:对他克莫司的药动学参数和不良反应等进行评价,为临床合理用药、个体化给药提供有益的信息和依据。方法:查阅他克莫司相关文献,对资料中的药物发生机制和常用药物进行分组,综合评价其临床应用。结果:他克莫司治疗窗窄、生物利用度低、个体差异大、联用时出现不良反应的几率较高。结论:临床上应高度重视他克莫司的合理使用,进行血液浓度监测应综合考虑联合用药等因素,实施个体化给药,保障用药安全。     

临床药师参与1例肾病综合征患儿个体化应用他克莫司的药学实践

临床药师参与1例激素依赖型肾病综合征患儿的药物治疗。患儿使用醋酸泼尼松联合他克莫司治疗过程中出现腹痛、腹泻不良反应,药师建议检测他克莫司血药浓度及CYP3A5基因型,并协助医生为患儿制订了他克莫司个体化给药方案。调整他克莫司给药方案后,患儿未再出现相关不良反应;出院随访他克莫司谷浓度均在目标范围内,3个月后尿蛋白转阴,病情稳定。临床药师参与肾病综合征患儿的用药管理,有助于提高患者用药的安全性及有效性。     

他克莫司软膏治疗面部脂溢性皮炎临床观察

目的:观察他克莫司软膏治疗面部脂溢性皮炎的疗效和不良反应.方法:应用0.1%他克莫司软膏治疗面部脂溢性皮炎28例,对临床疗效、不良反应、患者顺应性和医生评价进行了总结.结果:他克莫司软膏可以迅速缓解面部脂溢性皮炎的临床症状,由治疗前的12.30±2.01评分值下降至治疗后的6.12±3.19,近期临床效果满意.结论:他克莫司软膏用于治疗面部脂溢性皮炎疗效明显,个别病例出现局部瘙痒不良反应.     

他克莫司药理作用及临床疗效的研究进展

目的:总结他克莫司的药理作用和临床疗效,以期为临床合理使用提供参考。方法:查阅近期国内外相关文献,对他克莫司重要药理作用及疗效、药物相互作用、不良反应进行归纳、总结。结果:他克莫司具有免疫抑制、促神经再生作用,能有效治疗特应性皮炎、类风湿性关节炎、重症肌无力等疾病,与许多药物存在相互作用,可引起神经毒性、心肌增厚、牙龈增生等不良反应。结论:他克莫司临床应用广泛,明确其药理作用及疗效、药物相互作用、不良反应,为临床安全、合理使用提供参考。     

他克莫司致不良反应67例文献分析

目的：了解器官移植术后应用他克莫司所致不良反应的总体情况,分析其临床特征和影响因素,以促进临床合理用药。方法检索2000年至2013年维普数据、中国知网数据库、万方数据库等收载的国内期刊,检索到器官移植术后他克莫司致不良反应的文献42篇,对其中记载详细具体的67例病例资料进行统计、分析。结果他克莫司所致不良反应67例中,涉及神经系统毒性28例（占41.8%）,血糖异常12例（占17.9%）,电解质紊乱10例（占14.9%）,肝、肾及血液系统损伤分别为5,4,4例。其中神经系统不良反应预后最差（死亡3例,较严重后遗症2例）。他克莫司不良反应多发生在移植术后1周至3个月内（45例,占67.2%）,与该阶段他克莫司血药浓度偏高和药物相互作用密切相关。结论他克莫司个体差异大,易受血药浓度、联合用药、机体病理状态等因素的影响而发生不良反应,不良反应可累及多脏器或系统。用药期间应定期监测血浆他克莫司浓度和相关生化指标,警惕不良反应发生,及时调整用药,保证他克莫司应用的有效性和安全性。     

基于TDM与基因检测指导1例患者应用他克莫司的案例分享

目的 协助临床医师为患者实施个体化用药,提高患者药物治疗效果,也为临床药师开展个体化药学服务提供参考意见。方法 运用药物基因多态性联合血药浓度监测等技术对1例肺移植患者术后服用他克莫司出现症状样癫痫不良反应进行详细分析。结果 患者血清肌酐水平与他克莫司浓度高度相关(P<0.05),患者他克莫司的谷浓度与红细胞计数之间存在高度的相关性(P<0.05),该患者CYP3A5基因型为*3/*3,提示为慢代谢类型,他克莫司清除速率降低。结论 他克莫司属于窄治疗窗的药物,剂量或血药浓度的较小变化即可引起严重不良反应或治疗失败,且个体差异显著,根据该患者的监测,患者出现症状样癫痫很可能是由他克莫司引起的,而且他克莫司血药浓度与其导致的中枢神经系统不良反应不一定呈正相关。     

他克莫司软膏致痤疮11例

目的探讨他克莫司软膏导致痤疮的不良反应特点。方法对2008年8月~2009年6月间我科应用他克莫司软膏导致痤疮的临床资料进行整理,分析。结果他克莫司软膏致痤疮主要发生在青年,男性多于女性,多在用药2~3周后发生。表现为粉刺,炎性小丘疹,脓疱。结论对于他克莫司软膏致痤疮的规律及特点,应引起临床医师足够的重视,加强预防,以减少不良反应的发生。     

他克莫司软膏的药理及临床评价

他克莫司软膏为大环内酯类免疫调节剂,是治疗特应性皮炎(AD)的非皮质类固醇类外用制剂,他克莫司可抑制钙调磷酸酶的活性及阻止多种细胞因子生成,从而抑制T淋巴细胞活化,发挥药理作用。临床用于治疗AD疗效确切,不良反应较少。本文对他克莫司软膏的药理特性、临床应用和不良反应进行概述,供临床合理应用参考。     

酶放大免疫测定法动态监测肾病综合征患者他克莫司血药浓度

目的探讨动态监测肾病综合征患者他克莫司血药浓度的意义。方法肾病综合征患者26例,病理分型确定为系膜增生性肾炎或膜性肾病,均接受他克莫司联合糖皮质激素治疗3个月。观察临床疗效及不良反应发生情况。采用酶放大免疫测定法监测他克莫司全血谷浓度,根据测定结果调整剂量,并分析他克莫司血药浓度与临床疗效的相关性。结果治疗后,完全缓解12例,他克莫司血药浓度为(8.45±4.08)μg·L-1,4.37¹2.53μg·L-1;部分缓解9例,他克莫司血药浓度为(6.88±2.02)μg·L-1,最低为4.86μg·L-1;无效5例,他克莫司血药浓度为(3.43±1.55)μg·L-1,缓解率81%(21/26)。Spearmen等级相关分析显示,他克莫司血药浓度与临床疗效呈正相关(rs=0.623,P<0.01)。主要不良反应为中枢神经系统反应、血糖升高、感觉系统异常、胃肠道反应等,均不影响他克莫司的继续使用。结论他克莫司治疗肾病综合征时,临床疗效与血药浓度密切相关,全血谷浓度4.3712.53μg·L-1;部分缓解9例,他克莫司血药浓度为(6.88±2.02)μg·L-1,最低为4.86μg·L-1;无效5例,他克莫司血药浓度为(3.43±1.55)μg·L-1,缓解率81%(21/26)。Spearmen等级相关分析显示,他克莫司血药浓度与临床疗效呈正相关(rs=0.623,P<0.01)。主要不良反应为中枢神经系统反应、血糖升高、感觉系统异常、胃肠道反应等,均不影响他克莫司的继续使用。结论他克莫司治疗肾病综合征时,临床疗效与血药浓度密切相关,全血谷浓度4.37¹2.53μg·L-1内疗效满意。     

Calcineurin inhibitors in renal transplantation: what is the best option?

Recently, new calcineurin inhibitors, such as tacrolimus (FK-506) and microemulsion cyclosporin, have been approved for maintenance immunosuppression in renal transplant recipients and short-term outcomes have been accumulating. In the majority of patients, these calcineurin inhibitors have been used in combination with new immunosuppressive drugs, such as mycophenolate mofetil (MMF) or sirolimus. Under these circumstances, a comparison of cyclosporin and tacrolimus provides the answer to a very important controversial issue. Which drug should we choose in individual patients? In an attempt to answer this question, this review compared the use of tacrolimus and cyclosporin in modern immunosuppressive regimens, which have already been published in well designed clinical studies, and discusses how immunosuppression should be individualised in renal transplant patients.Overall, short-term patient and graft survival with cyclosporin microemulsion and tacrolimus is almost identical. The incidence of acute rejection is generally lower in tacrolimus/azathioprine- than in cyclosporin/azathioprine-treated patients. However, in conjunction with MMF, the difference in the incidence of acute rejection between tacrolimus- and cyclosporin-treated patients became smaller. Adverse events, such as hypertension, hyperlipidaemia and cosmetic changes (gum hypertrophy, hirsutism) seem to be less frequent in tacrolimus-treated than in cyclosporin-treated patients. Recent randomised studies showed that the incidence of post-transplant diabetes mellitus was almost identical between low-dose tacrolimus- and cyclosporin-treated patients. According to the data discussed in this review, the recommendation on the choice of calcineurin inhibitors at this moment is that either cyclosporin or tacrolimus can be used safely and effectively for patients without any risk factors. However, at our centre, we prefer tacrolimus to cyclosporin in patients with a high risk for rejection, such as those with ABO-incompatibility, delayed graft function, sensitisation, and African American race and some other risk factors, such as hypertension and hyperlipidaemia. Moreover, tacrolimus may be preferable to cyclosporin for women because of hirsutism and for children because of the steroid-sparing effect. We consider that cyclosporin should be chosen when patients experience tacrolimus-related adverse events, such as severe chest pain, tremor, gastrointestinal symptoms and encephalopathy. In conclusion, well tolerated and effective immunosuppression is feasible with both cyclosporin and tacrolimus. In the current immunosuppressive regimens, a calcineurin inhibitor, either tacrolimus or cyclosporin, is the essential basic standard immunosuppressant. Clinicians need to decide the best means of optimising therapy for individual patients, based on various risk factors, such as risk of rejection, i.e. sensitisation, delayed graft function and ABO-incompatibility, and some adverse events, such as hypertension, hyperlipidaemia and cosmetic changes.     

Tacrolimus: a further update of its pharmacology and therapeutic use in the management of organ transplantation

Tacrolimus (FK-506) is an immunosuppressant agent that acts by a variety of different mechanisms which include inhibition of calcineurin. It is used as a therapeutic alternative to cyclosporin, and therefore represents a cornerstone of immunosuppressive therapy in organ transplant recipients. Tacrolimus is now well established for primary immunosuppression in liver and kidney transplantation, and experience with its use in other types of solid organ transplantation, including heart, lung, pancreas and intestinal, as well as its use for the prevention of graft-versus-host disease in allogeneic bone marrow transplantation (BMT), is rapidly accumulating. Large randomised nonblind multicentre studies conducted in the US and Europe in both liver and kidney transplantation showed similar patient and graft survival rates between treatment groups (although rates were numerically higher with tacrolimus- versus cyclosporin-based immunosuppression in adults with liver transplants), and a consistent statistically significant advantage for tacrolimus with respect to acute rejection rate. Chronic rejection rates were also significantly lower with tacrolimus in a large randomised liver transplantation trial, and a trend towards a lower rate of chronic rejection was noted with tacrolimus in a large multicentre renal transplantation study. In general, a similar trend in overall efficacy has been demonstrated in a number of additional clinical trials comparing tacrolimus- with cyclosporin-based immunosuppression in various types of transplantation. One notable exception is in BMT, where a large randomised trial showed significantly better 2-year patient survival with cyclosporin over tacrolimus, which was primarily attributed to patients with advanced haematological malignancies at the time of (matched sibling donor) BMT. These survival results in BMT require further elucidation. Tacrolimus has also demonstrated efficacy in various types of transplantation as rescue therapy in patients who experience persistent acute rejection (or significant adverse effect's) with cyclosporin-based therapy, whereas cyclosporin has not demonstrated a similar capacity to reverse refractory acute rejection. A corticosteroid-sparing effect has been demonstrated in several studies with tacrolimus, which may be a particularly useful consideration in children receiving transplants. The differences in the tolerability profiles of tacrolimus and cyclosporin may well be an influential factor in selecting the optimal treatment for patients undergoing organ transplantation. Although both drugs have a similar degree of nephrotoxicity, cyclosporin has a higher incidence of significant hypertension, hypercholesterolaemia, hirsutism and gingival hyperplasia, while tacrolimus has a higher incidence of diabetes mellitus, some types of neurotoxicity (e.g. tremor, paraesthesia), diarrhoea and alopecia. Conclusion: Tacrolimus is an important therapeutic option for the optimal individualisation of immunosuppressive therapy in transplant recipients.     

他克莫司联合激素治疗儿童激素抵抗性肾病综合征临床研究

目的:研究他克莫司联合激素治疗儿童激素抵抗性肾病综合征的临床效果。方法:选取在我院治疗的30例激素抵抗性肾病综合征患儿随机分为试验组和对照组各15例,试验组采用他克莫司加激素治疗,对照组采用环磷酰胺加激素治疗,观察两组患儿治疗3个月及6个月后24 h尿蛋白定量、血浆白蛋白水平、临床疗效以及不良反应发生情况。结果:与对照组比较,试验组患儿治疗6个月后24 h尿蛋白定量水平降低,血浆白蛋白水平升高(P均<0.05);试验组患儿临床症状缓解有效率高于对照 组,差异有统计学意义(P<0.05);试验组患儿消化道症状、肝毒性、高血压等不良反应发生率为20.0%,低于对照组的66.7%, 差异有统计学意义(P<0.05)。结论:他克莫司联合激素治疗儿童激素抵抗性肾病综合征较环磷酰胺联合激素治疗的临床疗效 好且不良反应更少,值得临床推广应用。     

移植后高血压与他克莫司剂量及血药浓度的关系

目的:调查肾移植患者服用他克莫司后高血压的发生率,并探讨移植后高血压与他克莫司的服用剂量、血药浓度及血药浓度/剂量的相关性。方法:选取以他克莫司进行治疗的肾移植患者200例,测量患者的血压。然后从中随机抽取53例高血压患者和53例正常血压患者,待患者服用他克莫司至少3d后,运用微粒子酶免疫分析(MEIA)法测定他克莫司谷浓度,分析他克莫司剂量、血药浓度与血压水平的相关性,并比较两组患者的他克莫司剂量、血药浓度及血药浓度/剂量的差异。结果:在200例肾移植患者中,104例患者(52.0%)患有移植后高血压;他克莫司日剂量与患者的SBP呈正相关(r=0.216,P<0.05),而剂量与DBP,血药浓度与血压水平均无相关性;高血压组他克莫司的服用剂量明显高于正常血压组[(3.11±1.49)mg/d∶(2.42±1.07)mg/d,P<0.05];谷浓度两组间比较差异无统计学意义(P>0.05);高血压组患者的谷浓度/剂量明显低于正常血压组[(2.94±1.57)ng.d/mg.mL∶(3.95±3.02)ng.d/mg.mL,P<0.05]。结论:肾移植患者的SBP与他克莫司日剂量具有明显相关性,服用更高剂量他克莫司的患者更易发生高血压。     

肾移植患者MDR1C3435T基因多态性对他克莫司血药浓度/剂量比及疗效的影响

目的研究肾移植术后患者MDR1C3435T基因多态性对他克莫司（FK506）血药浓度／剂量比（C／D）及急性排斥反应和不良反应的影响。方法采用聚合酶链反应（PCR）和限制性内切片段长度多态性（RFLP）的方法检测肾移植患者MDR1C3435T基因型,比较不同基因型患者之间FK506的C／D值以及急性排斥反应、不良反应的差异。结果MDR1C3435T各基因型组间FK506的C／D值及急性排斥反应、不良反应均无显著性差异。结论MDR1C3435T基因多态性与肾移植患者FK506的C／D值及急性排斥反应、不良反应间无显著相关性。     

Effect of immunosuppressive agents on long-term survival of renal transplant recipients: focus on the cardiovascular risk

In the control of acute rejection, attention is being focused more and more on the long-term adverse effects of the immunosuppressive agents used. Since cardiovascular disease is the main cause of death in renal transplant recipients, optimal control of cardiovascular risk factors is essential in the long-term management of these patients. Unfortunately, several commonly used immunosuppressive drugs interfere with the cardiovascular system. In this review, the cardiovascular adverse effects of the immunosuppressive agents currently used for maintenance immunosuppression are thoroughly discussed. Optimising immunosuppression means finding a balance between efficacy and safety. Corticosteroids induce endothelial dysfunction, hypertension, hyperlipidaemia and diabetes mellitus, and impair fibrinolysis. The use of corticosteroids in transplant recipients is undesirable, not only because of their cardiovascular effects, but also because they induce such adverse effects as osteoporosis, obesity, and atrophy of the skin and vessel wall. Calcineurin inhibitors are the most powerful agents for maintenance immunosuppression. The calcineurin inhibitor ciclosporin (cyclosporine) not only induces these same adverse effects as corticosteroids but is also nephrotoxic. Tacrolimus has a more favourable cardiovascular risk profile than ciclosporin and is also less nephrotoxic. It has little or no effect on blood pressure and serum lipids; however, its diabetogenic effect is more prominent in the period immediately following transplantation, although at maintenance dosages, the diabetogenic effect appears to be comparable to that of ciclosporin. The diabetogenic effect of tacrolimus can be managed by reducing the dose of tacrolimus and early corticosteroid withdrawal. The effect of tacrolimus on endothelial function has not been completely elucidated. The proliferation inhibitors azathioprine and mycophenolate mofetil (MMF) have little effect on the cardiovascular system. Yet, indirectly, by inducing anaemia, they may lead to left ventricular hypertrophy. MMF is an attractive alternative to azathioprine because of its higher potency and possibly lower risk of malignancies. Sirolimus also induces anaemia, but may be promising because of its antiproliferative features. Whether the hyperlipidaemia induced by sirolimus counteracts its beneficial effects is, as yet, unknown. It may be combined with MMF, however, initial attempts resulted in severe mouth ulcers.     

低剂量氨氯地平联合特拉唑嗪治疗原发性高血压疗效观察

目的探讨低剂量氨氯地平联合特拉唑嗪治疗原发性高血压的临床效果及安全性。方法将原发性高血压患者60例随机分为观察组和对照组各30例。对照组给予常规剂量氨氯地平治疗,观察组给予低剂量氨氯地平联合特拉唑嗪治疗。治疗后观察2组临床疗效及不良反应。结果观察组显效率明显为53.33%高于对照组的20.00%(P<0.05)。2组治疗后收缩压及舒张压均较治疗前改善(P<0.05);且观察组收缩压及舒张压明显低于对照组(P<0.05)。且观察组无明显不良反应。结论低剂量氨氯地平联合特拉唑嗪治疗原发性高血压效果好,不良反应少,值得推广应用。     

他克莫司软膏治疗面部激素依赖性皮炎35例

目的探讨面部糖皮质激素依赖性皮炎的有效治疗方法。方法 72例面部糖皮质激素依赖性皮炎患者随机分为治疗组36例,外涂0.1%他克莫司软膏,2次/d;对照组36例外涂0.1%糠酸莫米松乳膏,1次/d,逐渐延长间隔至撤停,同时配合外涂0.3%多磺酸粘多糖乳膏1～2次/d。两组均口服左西替利嗪5mg/d,维生素C0.2g,3次/d,于治疗4周后判断疗效。结果两组各有35例完成治疗。治疗组有效33例（91.42%）,对照组有效24例（68.57%）,两组比较差异有显著性（P〈0.05）;治疗组局部不良反应11例、对照组8例,不良反应发生率无显著差异。结论 0.1%他克莫司软膏治疗面部糖皮质激素依赖性皮炎起效迅速、依从性较好、疗效显著。     

他克莫司软膏在儿童口周皮炎中的临床应用

目的分析0.03%他克莫司软膏在儿童口周皮炎治疗中的应用价值。方法儿童口周皮炎患儿70例,年龄2～14岁,随机分为观察组及对照组。观察组给予0.03%他克莫司软膏联合保湿软膏每日外用1次治疗。对照组采用保湿乳膏每日外用2次治疗。两组疗程均为4周。比较两组患儿治疗后1、2、4周治疗效果。结果观察组有效率高于对照组(P<0.01),观察组2周、4周的有效率明显高于1周(P<0.05)。观察组的药物不良反应发生率为13.9%(5/36),主要表现为轻微的红斑、烧灼及痒痛感。结论 0.03%他克莫司软膏治疗儿童口周皮炎疗效确切,安全性高。     

Treating erectile dysfunction in renal transplant recipients

Erectile dysfunction is common in male kidney transplant recipients. Interference with the physiology of erections can be attributed to recipient co-morbidities, the renal transplant operation, medication adverse effects, relationship problems and changes in mental health. A treatment-oriented evaluation of erectile dysfunction allows the development of treatment plans that are patient-specific. Hypo-gonadal men whose hormone parameters do not improve after renal transplantation may respond to testosterone replacement therapy. Use of recommended doses of the phosphodiesterase-5 inhibitor sildenafil does not significantly modify trough concentrations of the calcineurin inhibitors ciclosporin and tacrolimus or result in impaired renal allograft function. Tacrolimus has been shown to increase the peak concentration and prolong the elimination half-life of sildenafil in kidney transplant recipients. Daily administration of sildenafil has resulted in decreased blood pressure in kidney transplant recipients with treated hypertension and tacrolimus immunosuppression. Intracavernosal injections of alprostadil, with or without papaverine and phentolamine, are effective treatments for erectile dysfunction after renal transplantation and have not resulted in alterations of ciclosporin concentrations or in deterioration of renal function. Penile prostheses can be successfully implanted after pelvic organ transplantation without significant risk of infection.