地尔硫Zhou对肾移植受者环孢素A血药浓度影响

以荧光偏振免疫分析法测定肾移植受者环孢素Ａ血药浓度，并观察钙离子拮抗剂地硫Ｚｈｏｕ对２６例肾移植受者环孢素Ａ血药浓度的影响，同时以不同地尔硫Ｚｈｏｕ的２１例肾移植受者为对照。结果提示：地尔硫Ｚｈｏｕ与环孢素Ａ合用，可明显减少肾移植受者环孢素Ａ的用量。     

地尔硫zhuo对环孢素A肾毒性的防护及血药浓度的影响

目的：了解肾移植术后患应用地尔硫zhuo对环孢素A（CsA)血药浓度的影响及肾保护作用。方法：选用25例肾移植患分两组，治疗组加用地尔硫zhuo，采用荧光偏振免疫分析法测定CsA的全血谷浓度。结果：治疗组CsA的用量明显低于对照组，地尔zhuo能降低尿酸、血清肌酐、尿素氮水平。结论：地尔硫zhuo能减少CsA用量，防护CsA肾毒性，还可减少患费用。     

地尔硫对环孢素A肾毒性的防护及血药浓度的影响

目的 :了解肾移植术后患者应用地尔硫对环孢素A (CsA)血药浓度的影响及肾保护作用。方法 :选用25例肾移植患者分为两组 ,治疗组加用地尔硫 ,采用荧光偏振免疫分析法测定CsA的全血谷浓度。结果 :治疗组CsA的用量明显低于对照组 ,地尔硫能降低尿酸、血清肌酐、尿素氮水平。结论 :地尔硫能减少CsA用量 ,防护CsA肾毒性 ,还可减少患者费用     

合心爽对肾移植受者环孢素A血药浓度的影响

以荧光偏振免疫分析法测定肾移植受者环孢素A(CSA)的血药浓度。对20例CsA血药浓度谷值偏低的患者，加服合心爽(地尔硫卓)，结果表明：2周后CsA血药浓度明显升高，而CsA对肾功能的损害明显降低。     

地尔硫联合硝苯地平治疗肾移植并发高血压20例

目的：研究地尔硫、硝苯地平联合用于环孢素治疗肾移植并发高血压的长期疗效。方法：将40例经环孢素治疗的肾移植并发高血压患者随机分为治疗组和对照组各20例，治疗组给予地尔硫，每次30 mg，po，bid；硝苯地平每次10 mg，po，tid。对照组只给予硝苯地平，用法同治疗组。根据血压控制情况，调整治疗组地尔硫和对照组硝苯地平剂量。对患者进行＞2 a的临床观察，观察患者血药浓度及动脉血压、肾功能。结果：地尔硫干扰环孢素代谢，导致环孢素剂量降低40.0%，但未见其增强环孢素肾毒性。两组的平均血压水平相似，维持在正常范围内。两组肾功能差异无显著性(P＞0.05)。结论：地尔硫、硝苯地平联用于肾移植并发高血压症，安全有效，并能节约肾移植患者的费用。     

回顾性研究细胞色素P4503A5基因多态性对肾移植病人环孢素浓度的影响

目的 回顾性研究稳定期肾移植的病人在合用地尔硫卓后,CYP3A5基因多态性对环孢素(免疫抑制剂)浓度的影响.方法 用RFLP-PCR检测CYP3A5基因型;采用回顾性研究方法,分析肾移植病人CYP3A5基因型与环孢素血药浓度的关系.结果 合用地尔硫卓的病人,按CYP3A5不同基因型分组,3组病人之间的环孢素剂量和剂量调整浓度有明显差异;而不用地尔硫卓的病人进行分组后,环孢素剂量调整浓度也存在显著差异;环孢素剂量调整浓度,CYP3A5表达者显著低于不表达者组.结论 CYP3A5基因型对稳定期肾移植病人环孢素药代动力学有显著影响,且此相关性不受合用地尔硫卓影响.     

地尔硫(廾卓)对肾移植受者他克莫司用量及肾功能的影响

目的:观察地尔硫(廾卓)(Dil)减少肾移植受者他克莫司(Tac)用量、改善肾功能的效能.方法:肾移植术后3周,将Dil用于36例服用Tac的肾移植受者,以同期30例受者为对照,观察两组用药后1年内Tac用量和肾功能变化.结果:用Dil后1周,该组Tac血浓度平均升高56%,术后12月内,每例Tac用量平均较对照组少380 mg,两组Tac血浓度无显著差异(P＞0.05);12月时,Dil组血肌酐明显低于对照组(126.1±36.3 vs.145.8±41.5μmol·L-,P＜0.05).结论:Dil可明显减少肾移植受者的Tac用量,对移植肾功能亦具有保护作用.     

肾移植术后长期应用硫氮唑酮对环孢素A用量和肾功能的影响

目的:观察钙通道阻滞药硫氮唑酮(Dil)长期应用对肾移植受者环孢素A(CsA)用量和肾功能的影响。方法:将Dil用于67例服用CsA的肾移植受者,以同期59例肾移植受者为对照,调整2组CsA血药浓度在治疗窗范围内,观察2组用药后36mo内CsA用量以及血肌酐变化。结果:术后第12、24、36moDil组每例CsA用量较对照组同期平均少14353、9656、7817mg;术后12mo内2组血肌酐无显著性差异,以后对照组血肌酐水平上升较快,术后18mo～36mo,Dil组血肌酐水平明显低于对照组同期(P<0.05)。结论:肾移植术后长期应用Dil不仅可明显减少肾移植受者的CsA用量,而且可以改善移植肾功能。     

地尔硫（艹卓）提高肝移植受者他克莫司血药浓度的临床研究

目的评价地尔硫（艹卓）提高肝移植受者他克莫司血药浓度的疗效。方法选择116例肝移植术后长期口服他克莫司的受者,他克莫司和地尔硫（艹卓）同时口服的受者为试验组（58例）,单纯口服他克莫司的受者为对照组（58例）;检测两组全血他克莫司浓度,他克莫司用量及肝、。肾功能,进行分析。结果试验组服药后他克莫司血药浓度比服药前增加了（4．5&#177;0．5）μg／L,增幅达45．9％,用药前后比较差异有统计学意义（P〈0．01）;与对照组比较差异亦有统计学意义（P〈0．01）。试验组他克莫司用量明显减少,肝、肾功能无明显不良影响,无明显不良反应。结论地尔硫（艹卓）能明显提高肝移植受者他克莫司血药浓度,未发现明显不良反应。     

钙拮抗剂对环孢素A肾脏毒性的防护作用

本文报道在５５例肾移植术后患者中进行的一项随机对照比较实验，患者分别服用氨氯地平、拉西地平、硝苯吡啶、地尔硫Ｚｈｕｏ４种钙拮抗剂。结果发现钙拮抗地环孢素Ａ肾毒性具有防护作用，合并应用钙拮抗剂可以有效地降低患者的血清肌酐尿素氮水平、，且基本不发迹环孢素Ａ的血药浓度。与对照组相比，合并用氨氯地平、拉西地平、硝苯哟 尔硫草一，患者的血清肌酐水平下降的速度较快，与自身用药分别下降了４５．０％（Ｐ〈．０５）     

Clinical and Medicoeconomic Impact of the Cyclosporine-Diltiazem Interaction in Renal Transplant Recipients

The effect of the diltiazem-cyclosporine interaction on cyclosporine pharmacokinetics, pharmacodynamics, and pharmacoeconomics was studied in 10 recipients of renal allografts. Each subject was studied while receiving diltiazem 60 mg twice/day and while not taking the drug. After achieving steady-state conditions, cyclosporine and metabolite concentrations were determined in whole blood from samples drawn after the morning cyclosporine dose. After pharmacokinetic analysis, all patients were followed for 6 months during treatment with cyclosporine plus diltiazem or cyclosporine alone. Cyclosporine blood clearance decreased significantly after treatment with diltiazem (18.0–11.0 ml/minkg; p=0.008). The apparent volume of cyclosporine distribution also decreased significantly (4.26–2.62 L/kg; p<0.05). After 6 months, diltiazem had no effect on renal function indexes, and no apparent effect on immunosuppression. Alterations in cyclosporine clearance and apparent volume of distribution secondary to diltiazem result in dosage reduction and potential cost savings in transplant pharmacotherapy. The mean decrease in cyclosporine dosage requirements would produce a cost saving of $1520 or 28% per patient per year.     

Combination therapy with diltiazem plus CsA/MMF/Pred or CsA/Aza/Pred triple immunosuppressive regimens for use in clinical kidney transplantation in Northwestern China

Objective

The effects of diltiazem on 1692 kidney transplant recipients under the immunosuppressive regimen of cyclosporine A (CsA) in combination with either mycophenolate mofetil or azothioprine were assessed. The two treatment groups were compared for blood concentrations of CsA, the extent of acceptable dosage reduction for the maintenance of immunotherapy, potential effects of kidney protection, and promotion of graft function.

Method

We monitored changes of blood concentrations of CsA in the two different patient treatment groups for post-transplant graft function, episodes of acute rejection, and hepatic and renal toxicity in 1640 renal transplant recipients after treatment with diltiazem.

Results

In patients treated with the triple immunosuppressive regimen consisting of CsA, azothioprine, and prednisolone (Pred), the sub-group of patients receiving the diltiazem treatment saw a significantly reduced CsA dosage in comparison to the non-diltiazem group (control group 1) (P?<?0.05), but the blood concentrations of CsA of the diltiazem group were higher than those of control group 1 (P?<?0.01). Of the patients treated with CsA, mycophenolate mofetil, and Pred, the sub-group of patients also treated with diltiazem showed similar effects: CsA dosage was reduced (P?<?0.01) and the blood concentrations of CsA significantly increased (P?<?0.01) in comparison with those of control group 2. In addition, recovery time of graft function decreased to 4.7?±?1.8?days and 3.9?±?1.4?days in the two diltiazem treatment groups, respectively (P?<?0.05), and the rate of acute rejection decreased to 21 (p?<?0.05) and 7.9% (P?<?0.01), respectively.

Conclusion

In our cohort of renal transplantation patients, co-administration of CsA and diltiazem increased CsA blood concentration, thereby resulting in a reduction in its required dosage treatment, which lightened the patients?? economic burden while improving primary and long-term kidney function by promoting the recovery of graft function and decreasing hepatic and renal toxicity. The co-administration of diltiazem may also reduce the rate of acute rejection, especially in patients who also receive the triple immunosuppressive regimen consisting of CsA, mycophenolate mofetil, and Pred.     

环孢素对肾移植术后患者血脂影响的浓度依赖性(英文)

研究环孢素对血脂影响的浓度依赖性。方法对16例肾移植术后患者测定术前和术后血脂及环孢素血药浓度。结果在环孢素血药浓度与术后术前血浆胆固醇及甘油三酯差值之间无统计学相关性。但术后血浆胆固醇的增加在高浓度患者中具有统计学显著性(P>0.05)。结论环孢素对肾移植术后患者血脂的影响呈浓度依赖性。     

The effect of variable CYP3A5 expression on cyclosporine dosing, blood pressure and long-term graft survival in renal transplant patients

OBJECTIVE: Cyclosporine is extensively metabolized by cytochrome-P450 3A (CYP3A) enzymes in the liver and intestine including the CYP3A5 isoenzyme. CYP3A5 is also expressed in the kidney and has been implicated in blood pressure regulation. Appreciable expression of CYP3A5 occurs in carriers of the CYP3A5*1 allele, while the CYP3A5*3 allele is associated with low expression. We tested whether the presence of the CYP3A5*1 allele in renal transplant recipients and in donor kidneys influences cyclosporine dose requirements, blood pressure and long-term graft survival in renal transplant patients during chronic treatment with a cyclosporine-based immunosuppressive regimen. METHODS: We studied 399 Caucasian patients from our single-center registry with stable graft function for more than 10 weeks after transplantation. The genotypes for CYP3A5*1/*3 were determined by a TaqMan PCR method. Cyclosporine dose requirements, blood pressure and graft survival were analyzed in relation to the presence or absence of the CYP3A5*1 allele in recipients and donor kidneys. RESULTS: The CYP3A5*1 allele was found in 15.5% of the recipients and in 11.8% of the donor kidneys. The recipient CYP3A5*1 allele had no effect on cyclosporine dose and blood concentrations at trough with and without dose-adjustment. Blood pressure, number of antihypertensive compounds used for treatment and graft survival evaluated by Kaplan-Meier curves and Cox regression analysis were also not affected by the CYP3A5*1 allele either in recipients or donor kidneys. CONCLUSIONS: Cyclosporine dose requirements, blood pressure and long-term renal graft survival are not influenced by the CYP3A5*1 allele in Caucasian patients.     

Diltiazem increases blood concentrations of cyclized cyclosporine metabolites resulting in different cyclosporine metabolite patterns in stable male and female renal allograft recipients

1 Six male and six female stable renal allograft recipients under cyclosporine immunosuppression and without concomitant therapy with drugs known either to induce or inhibit CYP3A enzymes were included in the study and received 180  mg day⁻¹ diltiazem for 1 week in a two-period cross-over fashion. Cyclosporine (352±56  mg day⁻¹) was given in two daily oral doses. The daily doses were not changed during the study. Blood samples were collected for 12  h after receiving cyclosporine alone and after receiving diltiazem in addition for 1 week. Cyclosporine and nine of its metabolites were quantified using h.p.l.c.
2 Co-administration of diltiazem caused a 1.6 fold increase of the AUC(0,12  h) of cyclosporine and a 1.7 fold increase of the AUC(0, 12  h) of its metabolites. Analysis of the metabolite patterns showed an over-proportional increase of the AUC(0, 12  h) of the cyclized metabolites AM1c (2.6 fold) and AM1c9 (2.2 fold). The AUC(0, 12  h) values of cyclosporine and the hydroxylated metabolites increased less than two fold.
3 Differences of the AUC(0, 12  h) values of cyclosporine with and without diltiazem were significantly higher in female than in male patients ( P <0.02). The differences in the AUC(0, 12  h) values of the metabolites, especially AM1c, tended to be higher in female patients as well.
4 It is concluded that coadministration of diltiazem not only increases the blood concentration of cyclosporine but also those of its metabolites, leads to a shift of the metabolite pattern towards cyclized metabolites, and that the pharmacokinetic changes under diltiazem administration are more prominent in female than in male patients.     

Renal cyclosporine clearance in marrow transplant recipients: age-related variation

Cyclosporine is extensively metabolized in the liver and is subject to biliary elimination. Although only a small amount of the drug is eliminated unchanged in the urine, urine concentrations of the drug are much higher than blood or serum concentrations known to be associated with renal toxicity. Renal clearance (CL) of cyclosporine may be a sensitive correlate of nephrotoxicity, but renal CL studies of cyclosporine have not been reported in transplant patients. Therefore, we studied the renal CL of cyclosporine in 21 patients (median age, 27 yr) with hematologic malignancies undergoing allogeneic bone marrow transplantation. All patients received cyclosporine for prophylaxis or treatment of acute graft vs host disease. At the time of the study, all patients had normal renal function, as determined by serum creatinine concentration. Urine and serum cyclosporine concentrations were measured by high-performance liquid chromatography. Renal cyclosporine CL in different patients ranged from 1.8 to 79.8 mL/min. However, serial renal CL studies performed one week apart in two patients showed minimal intrapatient variability. Patients 25 years old or younger had a higher mean renal cyclosporine CL (39.7 mL/min) than older patients (17.9 mL/min) (P less than .05). These data show that renal cyclosporine CL is related to age and that renal CL in marrow transplant recipients is higher than the reported mean value in non-marrow-transplant patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

环孢素A血药浓度的影响因素探讨

目的：对影响CsA血药浓度的因素进行初步探讨。方法：采用FPIA法测定132例肾移植受者的CsA血药浓度，观察肝功能等对CsA血药浓度的影响。结果：肝功能异常，合并应用酮康唑、氟康唑、地尔硫、异烟肼及雷尼替丁等药物均可使CsA血药浓度显著升高，腹泻、喝浓茶等可使CsA血药浓度显著降低。此外，在术后早期部分患者CsA血药浓度与血RBC及HGB含量有显著正相关。结论：监测CsA血药浓度必须结合患者的实际情况具体分析，及时调整用药方案。     

不同抗排异组方对肾移植受者肝功能的影响

目的:了解环孢素(CsA)与硫唑嘌呤、霉酚酸酯、咪唑立宾、雷帕霉素及泼尼松不同组方治疗肾移植术后排斥反应时对患者肝功能的影响。方法:调查我院1995～2005年肾移植患者药历600份,分析应用不同CsA抗排异组方治疗前后生化指标的变化。结果:600例患者中109例发生了肝损害(18.2%)。肝功能异常组的CsA血药浓度显著高于肝功能正常组(P<0.05)。CsA与硫唑嘌呤、泼尼松合用时肝损害比率31%,高于其他三组。结论:CsA为主的联合抗排异治疗方案可导致肝损害,抗排异治疗时应尽量选用对肝损害较小的方案。     

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。     

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.