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     

环孢素对肾移植术后病人血胆固醇和甘油三脂的影响

目的：观察环孢素浓度和肾移植本身对血胆固醇及甘油三脂水平的影响。方法：在５０名肾移植术后病人，同时测定病人的环孢素、胆固醇及甘油三脂水平，按不同的环孢素峰、谷浓度将患者分组。并将术前和术后的水平进行比较。用ｔ检验进行统计学处理。结果：在肾移植前后，胆固醇水平有显著差异（Ｐ〈０．００１）；在肾移植术后，环孢素峰、谷水平过高或过低时，甘油三脂浓度有显著升高（Ｐ〈０．００１）。结论：服用环孢素可能是胆固     

环孢素对肾移植术后病人血胆固醇和甘油三脂的影响

目的 :观察环孢素浓度和肾移植手术本身对血胆固醇及甘油三脂水平的影响。方法 :在 50名肾移植术后病人 ,同时测定病人的环孢素、胆固醇及甘油三脂水平 ,按不同的环孢素峰、谷浓度将患者分组。并将术前和术后的水平进行比较。用t检验进行统计学处理。结果 :在肾移植前后 ,胆固醇水平有显著差异 (P <0 .0 0 1 ) ;在肾移植术后 ,环孢素峰、谷水平过高或过低时 ,甘油三脂浓度有显著升高 (P <0 .0 0 1 )。结论 :服用环孢素可能是胆固醇升高的原因之一 ,不能排除肾移植手术或其它药物如强的松、硫唑嘌呤对胆固醇的影响 ;环孢素浓度过高或过低可引起甘油三脂的波动可能是环孢素中毒或移植肾排斥影响到甘油三脂水平     

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.     

克拉霉素对肾移植患者环孢素A血药浓度的影响

目的 观察克拉霉素对环孢素A血药浓度的影响。方法 对l0例肾移植术后感染的患者，服用克拉霉素0．25g，每日2次，l0d后测其环孢素A血药浓度及肾功能，停用克拉霉素l0d后，复测环孢素A血药浓度及肾功能。结果 服用克拉霉素后环孢素A血药浓度与停用后相比较，浓度明显升高(P＜0．01)。结论 克拉霉素可提高环孢素A血药浓度，用于治疗肾移植术后感染时，应减少环孢素A剂量，并定期测定环孢素A血药浓度。     

肾移植患者术后牙龈增生与环孢素A浓度的相关性

目的:研究肾移植患者术后牙龈增生与其应用环孢素A(cyclosporine A)的关系.方法:记录肾移植患者术后药物使用情况,监测环孢素A血药浓度和唾液中浓度.结果:应用环孢素A的肾移植患者术后牙龈增生的发生率为28.9%.牙龈增生发生率随着术后年限的增加而增加.患者发生牙龈增生时环孢素A血药浓度与未发生的血药浓度差异无显著性(P＞0.05);而唾液中环孢素A浓度与未发生的血药浓度差异具显著性(P＜0.05).结论:肾移植患者术后牙龈增生与使用环孢素A的时间、唾液中环孢素A高浓度有关.     

肾移植术后患者血栓调节蛋白测定的临床意义

目的 研究肾移植术后患者血栓调节蛋白（ＴＭ）测定的临床意义。方法 采用ＥＬＩＳＡ法测定１９例肾移植术后患者中ＴＭ值。结果 肾移植术后正常组患者血浆中ＴＭ值显著低于环孢素肾毒性组和急性排斥组患者血浆中ＴＭ值，而环孢素肾毒性组环孢素血药浓度水平显著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。     

肾移植术后环孢素A血药浓度与肝毒性的关系

目的研究肾移植术后用环孢素(CsA)为主的免疫抑制剂治疗的患者CsA血药浓度和CsA致肝毒性的关系。方法分别用单克隆荧光偏振免疫分析法测定肾移植术后患者环孢素全血浓度;同时,酶速率法、酶循环及比色法监测丙氨酸氨基转移酶(ALT)活力及血清总胆红素(TBiL)、总胆汁酸(TBA)等肝功能指标。结果术前肝功能正常的46例肾移植受者中,确诊有16人发生了环孢素致药物性肝功能损害。结论移植术后应用环孢素的患者应密切监测CsA的血药浓度,并结合临床肝功能指标,调整环孢素的用量,以避免或减轻肝中毒。     

环孢素A对再生障碍性贫血病人血脂的影响分析

环孢素A(Cycloslporine,CsA)是一种高脂溶性环状十一肽大分子化合物。作为特异性免疫抑制剂,其对各型再生障碍性贫血以及肾移植术后病人的免疫排斥反应的确切疗效已获公认。免疫法测得环孢素A的全血有效血药浓度参考范围为100-400ng／ml,最小中毒浓度参考值为600ng／ml。有报道接受CsA可导致肾移植术后患者血脂增加,诱发心血管疾病。监测CsA血药浓度,研究CsA对血脂的影响,对降低再生障碍性贫血患者使用CsA后心血管疾病的发生,指导临床合理用药具有十分重要的意义。     

辛伐他汀治疗肾移植术后高脂血症患者(英文)

目的研究辛伐他汀对肾移植术后高脂血症患者的疗效。方法17例肾移植术后患者每日口服辛伐他汀10mg,持续时间1个月。口服辛伐他汀前后患者自肘静脉采血 ,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例肾移植术后患者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显著降至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显著升高至257.33±57.78ng/ml(P<0.01),在口服辛伐他汀的21例患者无1例观察到严重药物不良反应。结论小剂量的辛伐他汀能有效且比较安全地用于肾移植术后高脂血症患者     

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。     

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。     

肾移植术后患者对环孢素治疗的服药依从性调查

目的：评价肾移植术后患口服环孢素的服药依从性。方法：在肾移植术后患定期的环孢素血药浓度检查时，通过与患直接对话的方式，评价患的服药依从性，对统计结果进行分析。结果：服用环孢素油剂（赛斯平）的30例患，自认为每天坚持按时、定量口服药物的比例为53.3％（16/30），约33.3％（10/30）的患自认为有偶尔定量不准的现象，13.3％（4/30）的患有偶尔漏服药物的现象；而服用环孢素胶囊的30例患服药依从性大为改善，自认为每天坚持按时、定量服药的比例高达93.3％（28/30），只有6.7％（2/30）的患自认为会出现偶尔漏服药物的现象。结论：环孢素胶囊比环孢素油剂在肾移植术后患用药中具有更好的服药依从性。     

Longitudinal study of cyclosporine and lipids in patients undergoing bone marrow transplantation

The metabolic effects of intravenous cyclosporine on lipids and lipoproteins were studied in 29 allogeneic bone marrow recipients compared with 13 autologous bone marrow patients not requiring cyclosporine therapy. Patients were monitored continuously from 5 days prior to 27 days following transplantation; cyclosporine treatment was initiated 4 days before transplantation. Fasting lipid and lipoprotein levels were measured in serial blood samples throughout the study period. Nutritional supplementation, conditioning regimens and concomitant medications were not significantly different between groups. Furthermore, no significant differences in age, weight, lipid, or lipoprotein levels were found at baseline between the patient groups. Cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels remained unchanged in autologous patients. As compared with baseline values, plasma total cholesterol increased by an average of 26 percent in allogeneic transplantation patients receiving cyclosporine. Similarly, the ratio of low-density lipoprotein to high-density lipoprotein cholesterol was fourfold greater in those patients treated with cyclosporine compared to the autologous group. We conclude that cyclosporine appears to elevate cholesterol levels. Neither acute graft vs host disease nor changes in hepatic function could explain the differences in plasma cholesterol levels between groups.     

Atorvastatin does not affect the pharmacokinetics of cyclosporine in renal transplant recipients

Objective The aim of the present study was to evaluate the possible influence of atorvastatin on the pharmacokinetics of cyclosporine (INN ciclosporin) and its main metabolites, AM1 and AM9, in renal transplant recipients.Methods Whole blood samples from 18 renal transplanted patients on cyclosporine-based immunosuppressive therapy were collected prior to and after 4 weeks of treatment with atorvastatin (10 mg/day) and analysed with regard to both cyclosporine and its main metabolites, AM1 and AM9, using a specific chromatographic method with ultraviolet detection.Results On average, AUC_0-12 [area under the whole blood concentration versus time curve in the dosing interval (0–12 h)] of cyclosporine was 5% (–16, 5) (90% confidence interval) lower upon co-administration with atorvastatin. No statistically significant changes in any of the calculated pharmacokinetic variables [AUC_0-12, maximum whole blood concentration (C_max), whole blood concentration 12 h post dose (C₁₂), time to C_max (t_max), terminal half-life (t_1/2)] for cyclosporine or the two metabolites, AM1 and AM9, upon atorvastatin treatment were observed. On average, atorvastatin did not affect the ratio between the CYP3A4-mediated metabolite AM9 and cyclosporine, suggesting that atorvastatin does not affect the CYP3A4 metabolism of cyclosporine to any significant extent. However, the influence of atorvastatin on the ratio between AM9 and cyclosporine showed large interindividual variability.Conclusion The results of this study indicate that atorvastatin does not, on average, affect cyclosporine pharmacokinetics in renal transplant recipients.     

Single-dose cyclosporine pharmacokinetics in various biological fluids of patients receiving allogeneic marrow transplantation

The clinical usefulness of cyclosporine is hampered by dose-limiting toxicities to the kidney that are not predicted by drug levels in serum or whole blood. Because of its lipophilic nature, circulating plasma lipoproteins may play a role in drug disposition. This study characterized the pharmacokinetic parameters of a single 2-mg/kg i.v. infusion of cyclosporine in the whole blood, plasma, high-density (HDL), low-density (LDL), and very low-density (VLDL) lipoprotein fractions of nine patients before bone marrow transplantation. The dose- and protein-corrected area under the concentration-time curve in whole blood; plasma; and HDL, LDL, and VLDL compartments were 44.6 +/- 11.3, 19.2 +/- 2.4; 33.6 +/- 12.3, 49.0 +/- 19.9, and 17.5 +/- 9.0 ng h/ml, respectively. The mean half-life of the drug from the VLDL fraction was significantly less than from the other biologic fluids. The systemic clearance rate of cyclosporine was greater in the total plasma or VLDL fractions compared with whole blood and the HDL and LDL fractions. The HDL-cyclosporine clearance inversely correlated with the serum creatinine (r = -0.71; p less than 0.05) and total bilirubin levels (r = -0.76; p less than 0.05). The plasma half-life and volume of distribution directly correlated with fasting HDL cholesterol levels (r = 0.94 and 0.99; p less than 0.01). Correlations between pharmacokinetic parameters and lipid fractions suggest a role of lipids in the distribution of cyclosporine. These data may be useful in the development of guidelines for therapeutic drug monitoring of cyclosporine in the transplantation population.     

Influence of lovastatin on the pharmacokinetics, toxicity and immunologic response of cyclosporine in the obese Zucker rat

The combined use of lovastatin, a hypolipidemic agent effective in the reduction of cholesterol levels, and the lipophilic immunosuppressant, cyclosporine, was studied in the obese rat model. Pharmacokinetics, immunosuppressive activity, lipid levels, and creatinine clearances were compared between groups administered drug-free vehicle, lovastatin or cyclosporine alone, or concomitant cyclosporine and lovastatin. All groups were pre-treated with either oral lovastatin 2.5 mg kg-1 day-1 or propylene glycol vehicle for 1 week. Although no differences in renal function were observed in rat groups administered cyclosporine or lovastatin alone, there was a significant reduction in baseline creatinine clearance following combination therapy compared to placebo controls (70 +/- 18 vs 121 +/- 16 per cent of baseline; p less than 0.05). No differences in trough cyclosporine concentrations were observed between groups. Similarly, mean areas under the whole blood concentration-time profiles were not significantly different with or without concomitant lovastatin (61823 +/- 27295 vs 41470 +/- 10312 ng h ml-1; p = 0.13). No differences in systemic clearance or volume of distribution of parent cyclosporine were observed with combination therapy. Furthermore, lipid levels and T-lymphocyte activity were unchanged with the addition of lovastatin. Per cent increases in creatine kinase were significantly correlated with percentage drop in baseline renal function, suggesting the development of rhabdomyolysis. The present data support the interaction between cyclosporine and lovastatin observed clinically, resulting in acute renal dysfunction. Caution should be exercised in their combined use.     

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。     

Effects of curcumin on cyclosporine-induced cholestasis and hypercholesterolemia and on cyclosporine metabolism in the rat

Former studies have shown that curcumin, which can be extracted from different Curcuma species, is able to stimulate bile flow and to reduce hypercholesterolemia. We investigated in a subchronic bile fistula model the ability of curcumin to reduce cyclosporine-induced cholestasis and hypercholesterolemia. Male Wistar rats were daily treated with curcumin (100 mg/kg p. o.), cyclosporine (10 mg/kg i. p.), and a combination of curcumin with cyclosporine. After two weeks a bile fistula was installed into the rats to measure bile flow and biliary excretion of bile salts, cholesterol, bilirubin, cyclosporine and its main metabolites. Blood was taken to determine the concentration of these parameters in serum or blood. Cyclosporine reduced bile flow (-14 %) and biliary excretion of bile salts (-10 %) and cholesterol (-61 %). On the other hand, cyclosporine increased serum concentrations of cholesterol and triglycerides by 32 % and 82 %, respectively. Sole administration of curcumin led to a slight decrease of bile flow (-7 %) and biliary bile salt excretion (-12 %), but showed no effect on biliary excretion of cholesterol and serum lipid concentration. When curcumin was given simultaneously with cyclosporine, the cyclosporine-induced cholestasis was enhanced but the cyclosporine-induced hyperlipidemia was not affected. Neither the biliary excretion nor the blood concentration of cyclosporine was influenced by curcumin. The blood concentration of the main cyclosporine metabolites, however, was lowered by half while their biliary excretion was strongly increased by curcumin. From these results we conclude that curcumin is not able to prevent cyclosporine-induced cholestasis and hyperlipidemia after prolonged administration in bile fistula rats.