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91.
目的 系统评价肾移植术后免疫抑制剂他克莫司(Tac)与环孢素A(CsA)诱发高血糖的情况.方法 采用电子检索和手工检索进行文献初检,电子检索数据库有Medline database、中国期刊全文数据库、中国循证医学/Cochrane中心数据库(CEBM\CCD)和Cochrane图书馆,手工检索近期<中华器官移植杂志>等6种杂志.纳入涉及肾移植术后使用Tac与CsA出现高血糖的随机对照试验(RCT),数据由两名作者独立提取,纳入研究的方法学质量采用Jadad质量评分标准,使用Cochrane协作网提供的专用RevMan4.2软件进行统计数据分析.结果 初检中文文献11篇,外文文献157篇,最终纳入14篇RCT(13篇英文,1篇中文)涉及Tac与CsA治疗肾移植术后诱发高血糖发生率的对照统计.Meta分析结果显示,Tac诱发高血糖发生率在术后1年和2年均高于CsA,其差异具有统计学意义.结论 肾移植术后Tac诱发高血糖发生率高于CsA. 相似文献
92.
Entry-into-human study with the novel immunosuppressant SDZ RAD in stable renal transplant recipients 下载免费PDF全文
Neumayer HH Paradis K Korn A Jean C Fritsche L Budde K Winkler M Kliem V Pichlmayr R Hauser IA Burkhardt K Lison AE Barndt I Appel-Dingemanse S 《British journal of clinical pharmacology》1999,48(5):694-703
AIMS: To evaluate the tolerability of single oral SDZ RAD doses in stable renal transplant recipients and the pharmacokinetics of ascending SDZ RAD doses when coadministered with steady-state cyclosporin A microemulsion (Neoral). METHODS: This randomized, double-blind, placebo-controlled, sequential study involved 54 patients in six treatment groups; a different SDZ RAD dose (0.25, 0. 75, 2.5, 7.5, 15, 25 mg) was assessed in each group. Patients received a single oral dose of SDZ RAD (n=6) or placebo (n=3) with their usual Neoral dose. SDZ RAD and cyclosporin A pharmacokinetic parameters were determined. RESULTS: All SDZ RAD doses were well tolerated, with no discontinuations due to adverse events, serious adverse events, or deaths. Similar proportions of patients receiving SDZ RAD and placebo had at least one adverse event (44% and 50%, respectively). Mean changes in laboratory variables (baseline to endpoint) showed no clinically meaningful differences between SDZ RAD and placebo groups. SDZ RAD was absorbed rapidly and showed dose-proportional pharmacokinetics (dose: 2.5-25 mg), based on systemic exposure. Multiple postabsorptive phases in the pharmacokinetic profile indicate tissue distribution. The elimination half-life ranged from 24 to 35 h across the five highest dose groups. Pharmacokinetics were similar in men and women. Co-administration of escalating single oral SDZ RAD doses did not affect steady-state cyclosporin A pharmacokinetics. CONCLUSIONS: SDZ RAD was well tolerated; safety profiles of SDZ RAD and placebo were similar. SDZ RAD pharmacokinetics were dose-proportional across the range 2.5-25 mg in conjunction with cyclosporin A-based therapy, according to systemic exposure. Cyclosporin A pharmacokinetics were not affected by coadministration of single oral doses of 0.25-25 mg SDZ RAD. 相似文献
93.
环孢素A硬脂酸纳米球的实验研究 总被引:17,自引:0,他引:17
目的:探讨硬脂酸纳米球作为新型药物载体的可能性。方法:制备了硬脂酸纳米球(SA-NP),用电镜考察其形态,测定了各种理化特性;以环孢素A(CYA)为模型药物,制备了环孢素A硬脂酸纳米球(CYA-SA-NP);对其进行了红外光谱测定和差示扫描量热分析;建立了测定CYA-SA-NP和血中CYA的HPLC法。以市售CYA微乳型口服液为对照,测定了口服CYA-SA-NP在大鼠体内的药代动力学参数和相对生物利用度。结果:CYA-SA-NP的平均粒径为316.6nm,CYA的平均包封率为88.39%,CYA和硬脂酸之间无化学反应发生;CYA-SA-NP的相对生物利用度接近80%,而且达峰时间较晚,具有明显的缓释效果。结论:硬脂酸纳米球将可能成为一种新型的药物载体。 相似文献
94.
Ability of Doxorubicin-Loaded Nanoparticles to Overcome Multidrug Resistance of Tumor Cells After Their Capture by Macrophages 总被引:10,自引:1,他引:9
Soma CE Dubernet C Barratt G Nemati F Appel M Benita S Couvreur P 《Pharmaceutical research》1999,16(11):1710-1716
Purpose. Investigation of the ability of doxorubicin-loaded nanoparticles (NP/Dox) to overcome multidrug resistance (MDR) when they have first been taken up by macrophages.
Methods. The growth inhibition of P388 sensitive (P388) and resistant (P388/ADR) tumor cells was evaluated in a coculture system consisting of wells with two compartments. The tumor cells were seeded into the lower compartment, the macrophages were introduced into the upper part in which the drug preparations were also added.
Results. Doxorubicin exerted lower cytotoxicity on tumor cells in coculture compared with direct contact. In P388/ADR, NP/Dox cytotoxicity was far higher than that of free doxorubicin (Dox). Three different formulations of cyclosporin A (either free (CyA), loaded to nanoparticles (NP/CyA) or in a combined formulation with doxorubicin (NP/Dox-CyA)), were added to modulate doxorubicin efficacy. The addition of cyclosporin A to Dox increased drug cytotoxicity. Both CyA added to NP/Dox and NP/Dox-CyA were able to bypass drug resistance.
Conclusions. Despite the barrier role of macrophages, NP/Dox remained far more cytotoxic than Dox against P388/ADR. Both NP/ Dox + CyA and NP/Dox-CyA allowed to overcome MDR, but the last one should present greater advantagein vivo by confining both drugs in the same compartment, hence reducing the adverse effects. 相似文献
95.
目的 研究合用环孢素(Cys)前后硫唑嘌呤(AZP)血药浓度及药物动力学变化。方法 9只家兔灌胃法给硫唑嘌呤(20mg·kg-1)后,高效液相色谱法(HPLC)测定AZP和其主要代谢物6 巯基嘌呤(6 MP)的血药浓度,1wk后,灌胃给Cys(15mg·kg-1,qd)共4d,并于d4灌胃给Cys后lh再以同样方式给AZP,同法测定AZP和6 MP血药浓度,以3P87药物动力学程序拟合药物动力学参数。结果 正常家兔合用环孢素后,6 MP的Vc升高,由合用前(159-1±24-2)升至合用后(269-9±118-0)L·kg-1(P<0-05),CL升高,由(1-6±0-4)升至(3-2±2-0)L·min-1·kg-1(P<0-05),AUC降低,由(77-97±26-02)降至(47-01±22-70)min·μmol·L-1(P<0-05)。其他药动学参数变化差异无显著性。结论 合并用药可引起Vc、CL升高,AUC降低。 相似文献
96.
目的:观察更昔洛韦对肾移植患者环孢菌素A药代动力学参数的影响,以促进临床合理用药,提高肾移植存活率。方法:分别对10例肾移植患者单用环孢菌素A与合用更昔洛韦后环孢菌素A的药代动力学参数进行研究和评价,采用荧光偏振免疫法测定各时刻环孢菌素A血中浓度,3P87程序拟合药代动力学参数,t检验比较组间差异。结果:合用更昔洛韦后,环孢菌素AKe,t1/2(Ka)分别由单用组的(0.16±0.04)h-1和(1.39±0.76)h降至(0.09±0.05)h-1和(0.50±0.32)h(P<0.05),tmax由(3.67±0.77)h-1减至(2.00±0.78)h-1(P<0.01),t1-2(Ke)由(4.08±1.85)h-1增至(10.51±6.42)h-1,峰浓度cmax平均升高27%。结论:更昔洛韦使肾移植患者对环孢菌素A的吸收显著加快,而使环孢菌素A在体内的消除减慢,对血中环孢菌素A的峰浓度也有一定影响,揭示临床调整用药方案。 相似文献
97.
H. J. Schlitt U. Christians J. Bleck K. Kohlhaw B. Ringe H. Bunzendahl K. F. Sewing K. Wonigeit R. Pichlmayr 《Transplant international》1991,4(1):38-44
The aim of this study was to analyse the immunosuppressive contribution of cyclosporin metabolites in liver-grafted patients. Therefore the immunosuppressive potency of 17 metabolites, alone and in combination, was tested in human mixed lymphocyte cultures, and the results were correlated with metabolite blood levels in liver-grafted patients. Of the 17 metabolites tested only six highly lipophilic metabolites showed a detectable immunosuppressive activity of up to 10% of the activity of cyclosporin; the effect of combining metabolites was additive. For calculation of the in vivo activity, blood levels of seven major cyclosporin metabolites were determined in liver-grafted patients with normal liver function (group A, 43 episodes) and with severe hyperbilirubinaemia (group B, 66 episodes). Both patient groups had comparable levels of parent drug (122.9±17.4 vs. 111.1±23.5 ng/ml by HPLC) and similar blood levels of the highly lipophilic metabolites 17, 1 and 18. By contrast, blood levels of the less lipophilic metabolites 8, 9, 26 and 203–218 were substantially increased in group B (P<0.05). High overall metabolite blood levels in group B were also indicated by a non-specific monoclonal RIA (520±199 ng/ml for group A vs. 1318±407 ng/ml for group B). Despite the very high levels in group B, however, the overall contribution of the metabolites to immunosuppression was similar in both groups (12.6±5.0% for group A vs. 13.8±5.6% for group B). These findings indicate that, despite a marked accumulation of cyclosporin metabolites in patients with severe cholestatic liver dysfunction, their immunosuppressive contribution remains low. This suggests that for assessment of the immunosuppressive potency of cyclosporin therapy monitoring of parent drug levels is necessary and sufficient. Since a variety of non-immunological effects of high metabolite levels cannot be excluded, however, additional non-specific measurements may, nevertheless, be useful in patients with severely disturbed liver graft function. 相似文献
98.
J. Ruutiainen R. Salonen P. Halonen M. Panelius J. Eskola A. Salmi 《Acta neurologica Scandinavica》1991,83(1):52-54
Twenty-six acute exacerbations in 26 patients with early definite multiple sclerosis (MS) were treated with oral cyclosporin-A (CyA) or oral prednisolone in a double-blind, controlled and randomized trial. The duration of the treatment was 6 weeks. All of the patients showed improvement during the treatment. There were no differences in outcome between patients on CyA (7.5 mg/kg) or prednisolone (decreasing doses from 0.8 mg/kg) during the 6 week treatment. However, the improvement of clinical signs 3 months after the treatment was slightly greater in the prednisolone group. The drugs did not have significant side-effects. There was no fluctuation in the CD4/CD8 ratio during the follow-up. The two treatment groups did not differ from each other in respect to the number of CD3 (T3), CD4 (T4), CD8 (T8), CD14 (monocytes), CD20 (B cells) or CD25 (interleukin-2 receptor positive cells). The number of active T cells with the interleukin-2 receptor was high in the beginning of the exacerbation but it decreased during the treatment. To conclude, the effects of CyA and prednisolone were comparable in the treatment of acute MS relapses. 相似文献
99.
100.
The efficacy of plaque control as a means of preventing cyclosporin-induced gingival overgrowth was assessed in 27 adult renal transplant patients. After baseline examination, patients were randomly allocated to receive intensive oral hygiene instructions, scaling and root planing (OH group) or no treatment (no treatment group). Gingival condition was assessed 6 months after baseline and changes in gingival form were related to various periodontal and pharmacokinetic measures. In both treatment groups, there was a significant increase (P less than 0.05) in gingival hyperplasia scores at 6 months. In the OH group, plaque scores were significantly lower (P less than 0.05) at 6 months, whereas in the no treatment group, a significant increase in plaque scores, gingival inflammation and probing depths was observed at 6 months. Dosages of cyclosporin, whole blood concentrations of cyclosporin, baseline gingival index, hyperplasia scores, and 6-month plaque index were not important determinants for the increase in gingival over-growth in both treatment groups. It is concluded that attention to plaque control and the removal of local irritants is of some benefit for the gingival health of cyclosporin-treated adult renal transplant patients, but these measures alone did not prevent gingival overgrowth. Pharmacokinetic variables of cyclosporin and various periodontal measures were not good predictors of cyclosporin-induced gingival changes. 相似文献