影响心脏移植术后患者环孢素A血药浓度的因素分析

目的:探讨心脏移植术3个月后,影响患者环孢素A(CsA)血药浓度的因素。方法:某医院先后采用双腔静脉法进行了10例同种异体心脏移植,术后均采用CsA口服联合免疫抑制治疗。采用多元线性回归回顾性分析同一患者在不同时期的CsA剂量、膳食结构、体重变化、肝功能、合用影响CsA代谢的药物对CsA血药浓度的影响。结果:同一患者在不同时期内CsA剂量、患者饮食结构和合用药物对CsA血药浓度的影响较大。结论:心脏移植患者术后应讲究平衡饮食,不要随便更改饮食结构。合用其他药物应咨询心脏或免疫科医生并检测CsA浓度。     

肾移植受者环孢素A血药浓度监测的回顾分析

目的 探讨影响肾移植受者术后环孢素A(CsA)血药浓度的因素。方法 197例肾移植受者术后口服CsA达稳态时,用荧光偏振免疫分析法(FPIA)测定其全血CsA浓度,分析各种因素对CsA血药浓度的影响。结果 CsA的个体差异较大,剂量、术后时间、肝肾功能、胆汁排泄、食物吸收、合并用药甚至于患者的性别、年龄等因素都可以影响CsA的吸收、代谢、排泄。结论 每个病人的病情、用药情况都不尽相同。监测CsA血药浓度时必须结合患者的实际情况作具体分析,及时调整用药方案。确保正确地指导临床合理用药,提高治疗水平。     

环孢素A血药浓度的HPLC测定方法

目的：建立环孢素A血药浓度的HPLC测定方法。方法：采用反相HPLC的方法,血样经乙醚萃取,正己烷洗脱等处理后测定。采用DiamonsilTMC18色谱柱,流动相为乙腈-水（74：26,V/V）,流速为1ml/min,柱温为70℃,检测波长为210nm。结果：环孢素A血药浓度在50~1000ng/ml范围内线性关系良好,R2=0.9997,低中高三种浓度的提取回收率为70.01%~75.00%,方法回收率为98.93%~103.08%,日内精密度RSD为0.84%~4.76%,日间精密度RSD为5.38%~9.87%。结论：该方法快速灵敏准确,可用于环孢素A血药浓度的监测。     

环孢素A血药浓度监测相关实验室检测研究进展

环孢素A(cyclosporine A, CSA)属于多肽类的免疫抑制剂,广泛用于器官移植和组织移植,具有很好的免疫抑制活性。因其口服吸收差,体内代谢个体差异大,其浓度与疗效和毒性相关,且治疗窗窄,故需对CSA进行血药浓度监测。同时,CSA在体内的代谢产物较多,并且体外实验证明,其代谢产物又各具有不同的活性。市面上CSA血药浓度检测方法较多,原理各不相同,对不同检测方法的选择成为临床及实验室的一大难题。本文针对目前CSA血药浓度检测方法进行综述,并对引起CSA血药浓度差异的药物代谢基因进行说明,望对临床及实验室关于CSA血药浓度的解读有所帮助。     

环孢素A治疗难治性肾病综合征的临床观察

目的：探讨环孢素A用于治疗难治性肾病综合征的临床疗效与价值。方法：选取2010年1月-2013年12月本院儿科确诊的难治性肾病综合征患者共46例,对所有患者使用环孢素A进行治疗,并对其治疗后每3个月实验室检查指标、症状改善及复发人数等情况进行记录。结果：治疗后,患者各项检查指标均显著优于治疗前,比较差异统计学意义（P〈0.05）;治疗后不同病理类型疾病缓解率分别为75.0%,91.7%,88.9%,治疗效果显著;患者中,有2例微小病变患者、1例系膜增生性肾小球肾炎患者使用半年环孢素A后无效,病情迁延不愈,调整剂量后再次使用环孢素A,疾病均得到一定控制,疗效较好。结论：使用环孢素A对难治性肾病综合征进行治疗疗效显著,可发挥免疫抑制作用,在疾病治疗中抑制自身免疫反应,有效减少炎性反应。短期疗效显著,不良反应较少,安全系数较高。可在短时间内缓解患者症状,有效改善蛋白尿且长期预后较好。用药时严格检测药物血药浓度及肝肾功能可提高用药安全性,降低不良反应发生率。     

环孢素A联合小剂量激素治疗特发性膜性肾病31例临床分析

目的特发性膜性肾病（IMN）是肾病综合征的主要病理类型之一,因其对激素不敏感而易于成为难治性肾病综合征．本文通过观察环孢素A＋小剂量激素治疗IMN的临床疗效,探讨其治疗。方法观察31例经肾活捡证实诊断的IMN患者对环孢素A（CsA）＋小剂量激素的治疗反应。治疗方法为环孢素A2～3mg·kg^-1·d^-1（CsA血药浓度120～150mg／L）8周,继以1～2mg·kg^-1·d^-1（CsA血药浓度80-100mg／L）维持12～24个月：泼尼松给予0．25mg·kg^-1·d^-1开始,8周后每2周逐渐减量至0125mg·kg^-1·d^-1维持;观察尿蛋白排出量、血浆蛋白和症状体征。结果完全缓解率52％,部分缓解率35％,未缓解13％,有效率达87％.结论环孢素A联合小剂量激素治疗IMN疗效肯定。     

环孢素A用于临床治疗儿童难治性肾病综合征的疗效观察

目的 探讨环孢素 A(cyclosporin A )在临床上用于小儿难治性肾病综合征的用药指征与治疗价值。方法 选2015年3月至2017年2月本院儿科确诊的难治性肾病综合征患儿共33例,对其应用环孢素A治疗,并对比其治疗后半年临床症状缓解程度、肝肾功能等生化指标及尿蛋白情况。结果 治疗后患儿临床表现、肝肾功能生化指标及尿蛋白指标均优于治疗前;治疗后,不同病理类型的患者临床症状缓解率达75%以上,疗效明显。结论 临床应用环孢素A治疗儿童难治性肾病综合征疗效显著,其免疫抑制作用可显著降低全身炎症反应。在非免疫抑制方面其可起到减少肾脏血流,降低肾小球滤过压力,改善蛋白尿作用。谨慎把握环孢素A 的药物适应证、剂量,并检测药物浓度,定期检测患儿肝肾功能及各生化指标,可充分发挥药物疗效,并将其不良反应降至最低。     

环孢素A联合小剂量激素治疗特发性膜性肾病31例临床分析

目的特发性膜性肾病(IMN)是肾病综合征的主要病理类型之一,因其对激素不敏感而易于成为难治性肾病综合征,本文通过观察环孢素A+小剂量激素治疗IMN的临床疗效,探讨其治疗。方法观察31例经肾活检证实诊断的IMN患者对环孢素A(CsA)+小剂量激素的治疗反应。治疗方法为环孢素A2～3mg·kg-1·d-1(CsA血药浓度120～150mg/L)8周,继以1～2mg·kg-1·d-1(CsA血药浓度80～100mg/L)维持12～24个月;泼尼松给予0.25mg·kg-1·d-1开始,8周后每2周逐渐减量至0.125mg·kg-1·d-1维持。观察尿蛋白排出量、血浆蛋白和症状体征。结果完全缓解率52%,部分缓解率35%,未缓解13%,有效率达87%。结论环孢素A联合小剂量激素治疗IMN疗效肯定。     

关于局部应用环孢素A聚乳酸微球的性状及释药研究

目的：研究分析局部应用环孢素A聚乳酸微球的性状以及释放情况,为临床治疗和理论研究提供参考依据。方法：使用溶剂挥发方式对环孢素A聚乳酸微球进行制备,在这个过程中,研究环孢素A聚乳酸微球的分散情况、直径以及外观还有药性释放的情况,并且结合研究对比全身和局部在给药以后气管中具有的环孢素A的浓度情况。结果：通过研究探讨,对环孢素A聚乳酸微球在形态、平均直径、载药量、释放药性情况、在气管中维持的药物浓度以及跨距等有了相关了解,其中形态相对完整,平均直径为17.965μm,载药量为（33.6±0.2）%,药性释放方面,在30天内释放的药性累加起来为40.4%,局部应用环孢素A聚乳酸微球以后半个月之内可维持较高的浓度,但是半个月以后药物的浓度值维持在180ng/ml。结论：局部应用环孢素A聚乳酸微球可使药物浓度维持时间较长,药性释放较慢,优于全身应用的效果,在临床应用中可以考虑使用。     

环孢素A血药浓度监测研究进展

环孢素(Cyclosporin,CsA)是目前临床上常用的强效免疫抑制剂,广泛用于器官移植术后的抗排异反应和某些自身免疫性疾病的治疗,由于CsA的生物利用度和药动学参数个体差异较大,治疗指数低,血药浓度又受多种因素影响,因此在治疗过程中进行血药浓度监测非常重要.本文就近年来与CsA血药浓度监测有关的一些研究作一综述,以期为临床合理使用CsA提供有益的资料.     

红细胞压积对环孢霉素浓度检测影响的研究

目的探讨不同红细胞压积对环孢霉素浓度的影响。方法用六个不同压积的全血,将环孢霉素标准液加入上述血液中,使每个压积的血液含有高低两种不同浓度的环孢霉素,利用高效液相色谱法(HPLC)和酶联免疫分析比色法(EMIA)两种方法测定不同红细胞压积中环孢霉素的血药浓度。结果随着红细胞压积的增大,环孢霉素的回收率逐渐增高,高效液相色谱法在100ng/ml环孢霉素检测的最高平均回收率为110.6%,最低平均回收率为77.2%;在400ng/ml环孢霉素检测的最高平均回收率为114.9%,最低为82.0%;酶联免疫分析比色法在100ng/ml环孢霉素检测的最高平均回收率为115.1%,最低为80.4%;在400ng/ml环孢霉素检测的最高平均回收率为119.1%,最低为85.4%。且高效液相色谱法比免疫学方法测得的环孢霉素浓度低。结论两种方法具有良好的相关性,且高效液相色谱法低于免疫分析法;红细胞压积对环孢霉素浓度影响因素较大。     

Chloroquine and desethylchloroquine concentrations during regular long-term malaria prophylaxis

The concentrations of chloroquine and desethylchloroquine in the blood of 10 healthy adult Swedish volunteers who had been taking 310 mg chloroquine base once a week for at least 8 months for malaria prophylaxis were measured. Samples of capillary whole blood from the volunteers were dried on filter-paper and the drug and its principal metabolite determined by a specific high-performance liquid chromatography (HPLC) method. The day after taking the drug, the mean concentration of chloroquine and desethylchloroquine in whole blood were 1305 nmol/l and 915 nmol/l, respectively, and immediately before the next weekly dose, 489 nmol/l and 384 nmol/l, respectively. These are considered to be greater than the minimum inhibitory concentrations for susceptible strains but less than the maximum tolerated concentrations. The dosage of chloroquine recommended roughly 40 years ago for regular long-term prophylaxis should therefore not be changed.     

矽宁在人体内的药代动力学研究

建立了高效液相色谱法测定人体全血中矽宁浓度。该法最低检测浓度为０．０１ｍｇ／Ｌ，平均回收率为９６．３％±０．４％，日内及日间的精密度（ＣＶ）分别为５．９％及８．９％。全血中矽宁浓度在０．０４～１２００ｍｇ／Ｌ时呈良好的线性关系。健康男性志愿者７名，口服单剂量矽宁１００ｍｇ后，其药代动力学过程符合二室一次吸收模型。该药在消化道内吸收较快，滞后时间为０．１８８ｈ，血浆浓度达峰时间为０．６９５ｈ，全血消除相半衰期（Ｔ）为６．２６３ｈ，表现分布容积为０．３ｍＬ／ｋｇ。     

Pentamidine concentrations in plasma, whole blood and cerebrospinal fluid during treatment of Trypanosoma gambiense infection in C?te d'Ivoire.

Pentamidine concentrations in plasma, whole blood and cerebrospinal fluid (CSF) were determined in 11 patients with Trypanosoma gambiense infection without involvement of the central nervous system in C?te d'Ivoire. Blood samples were drawn during a 48 h period after the first and last dose of pentamidine dimesylate given as 10 intramuscular injections on alternate days. Maximum plasma concentrations were generally attained within one hour after injection but varied extensively (420-13420 nmol/litre). The median plasma concentration 48 h after the last dose was approximately 5 times higher than that after the first dose. The ratio between whole blood and plasma concentration was approximately 2. Small amounts of the drug were found in the CSF after the last dose. The findings showed inter-individual differences in the pharmacokinetics of pentamidine. The currently recommended daily dose regimen could be questioned, as drug accumulation was pronounced. All patients were cured and the concentrations attained should be considered as parasiticidal. Further studies on the kinetics and distribution after single and multiple doses of pentamidine as well as studies on the possible relationship between adverse effects and plasma concentrations are, however, needed.     

Citrus grandis peel increases the bioavailability of cyclosporine and tacrolimus, two important immunosuppressants, in rats

Citrus grandis peel (CGP) is a beverage ingredient and a medicinal herb in Oriental countries. Cyclosporine and tacrolimus, important immunosuppressants with narrow therapeutic windows, are widely used in transplant patients. This study investigated the effects of co-administering CGP on the bioavailability of cyclosporine and tacrolimus. Male Sprague-Dawley rats were orally administered tacrolimus or cyclosporine with and without CGP. The concentrations of cyclosporine and tacrolimus in blood were assayed by monoclonal fluorescence polarization immunoassay and microparticle enzyme immunoassay, respectively. P-glycoprotein- and cytochrome P 450 3A4 (CYP3A4)-associated mechanisms were investigated by using everted rat intestinal sac and recombinant CYP3A4 isozyme. The results showed that CGP significantly increased the bioavailability of cyclosporine and tacrolimus by 100.0% and 234.7%, respectively. Ex vivo studies indicated that the interaction was mediated by the inhibition of CYP3A4. We suggest that CGP is contraindicated for transplant patients treated with cyclosporine or tacrolimus to minimize the risk of intoxication.     

Further characterization of a furanocoumarin-free grapefruit juice on drug disposition: studies with cyclosporine

BACKGROUND: We previously established furanocoumarins as mediators of the interaction between grapefruit juice (GFJ) and the model CYP3A4 substrate felodipine in healthy volunteers using a GFJ devoid of furanocoumarins. It remains unclear whether furanocoumarins mediate drug-GFJ interactions involving CYP3A4 substrates that are also P-glycoprotein substrates. OBJECTIVE: The effects of furanocoumarin-free GFJ on drug disposition were further characterized by using the dual CYP3A4/P-glycoprotein substrate cyclosporine. DESIGN: By randomized crossover design, 18 healthy volunteers received cyclosporine (5 mg/kg) with 240 mL orange juice (control), GFJ, or furanocoumarin-free GFJ. Blood was collected over 24 h. Juice treatments were separated by > or = 1 wk. The effects of diluted extracts of each juice and of purified furanocoumarins on [3H]cyclosporine translocation in Caco-2 cells were then compared. RESULTS: The median (range) dose-corrected cyclosporine area under the curve and the maximum concentration with GFJ (P < or = 0.007), but not with furanocoumarin-free GFJ (P > or = 0.50), were significantly higher than those with orange juice [15.6 (6.7-33.5) compared with 11.3 (4.8-22.0) x 10(-3) h/L and 3.0 (1.6-5.8) compared with 2.4 (1.1-3.1) mL(-1), respectively]. The median time to reach maximum concentration and terminal elimination half-life were not significantly different between the juices (2-3 and 7-8 h, respectively; P > or = 0.08). Relative to vehicle, the GFJ extract, orange juice extract, and purified furanocoumarins partially increased apical-to-basolateral and decreased basolateral-to-apical [3H]cyclosporine translocation in Caco-2 cells, whereas the furanocoumarin-free GFJ extract had negligible effects. Reanalysis of the clinical juices identified polymethoxyflavones as candidate P-glycoprotein inhibitors in orange juice but not in GFJ. CONCLUSIONS: Furanocoumarins mediate, at least partially, the cyclosporine-GFJ interaction in vivo. A plausible mechanism involves the combined inhibition of enteric CYP3A4 and P-glycoprotein.     

选择性制备浓缩血小板成分制品的效果分析

目的通过研究制备前检测待制备全血的血小板计数,选择性制备浓缩血小板(platelet concentrates,PC),探讨提升制备PC效率的方法。方法采集124例健康献血者全血400 ml,采用白膜法分离制备PC。随机分为2组,每组62例。对照组:新鲜采集的全血在6 h之内直接分离制备PC;实验组:新鲜采集的全血在6 h之内先进行血小板计数,剔除计数<130×10^9/L的全血之后进行PC的分离制备。检测PC的血小板计数、红细胞混入量与p H值。结果实验组制备的PC的血小板计数高于对照组,二者差异有统计学意义(t=2. 330 8,P <0. 05)。结论在制备前检测待制备全血的血小板计数,选择血小板计数≥130×10^9/L的全血制备能够显著提高PC计数合格率,提升PC的制备效率。     

Field evaluation of the use of an ELISA to detect chloroquine and its metabolites in blood, urine and breast-milk

The evaluation of an enzyme-linked immunosorbent assay (ELISA) for chloroquine and its metabolites in blood, urine and breast-milk is reported. ELISA blood levels, following standard treatment with chloroquine of pregnant and non-pregnant women, showed mean values comparable to other analytical methods. Blood chloroquine concentrations were estimated at day 0, 350-400 ng/ml; day 2, 1000-1500 ng/ml; day 14, 350-400 ng/ml; day 28, 180-350 ng/ml. In a separate sample a significant association was observed between history of chloroquine use in the previous 2 weeks and blood ELISA values (P less than 0.01). Mean ELISA values in breast-milk were higher than in corresponding whole blood samples. High concentrations of chloroquine in urine were observed. There was a weak association of the ELISA of urine and blood samples collected at the same time (P = 0.076). This study confirms the low sensitivity (less than 55%) of the Dill-Glazko test in urine, which is 100-1000 times less sensitive than the ELISA; the latter can detect 10-20 ng chloroquine per ml. A cut-off value for blood positivity 2 weeks following therapeutic drug ingestion was determined (40% ELISA inhibition), which can be used to make decisions about subject selection in drug sensitivity tests or population surveys. There are several advantages with the ELISA under field conditions. These include direct measurement of whole blood concentration; avoidance of problems of urine collection; suitability of finger-prick samples, especially with young children; application to population surveys to monitor drug use; and selection of subjects for drug sensitivity tests and monitoring of blood levels during in vivo tests.