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。     

头孢替安钠与呋塞米合用对大鼠肾功能的影响

目的:评价头孢替安钠与呋塞米合用的安全性,为临床用药提供参考。方法:设空白组、头孢替安钠500 mg·kg-1·d-1组、头孢替安钠500 mg·kg-1·d-1+呋塞米15 mg·kg-1·d-1组,给药12d后检测大鼠肾脏结构,以及血清尿酸、肌酐、尿素氮,大鼠尿α1微球蛋白,β2微球蛋白等水平。结果:头孢替安钠500 mg·kg-1·d-1给药后对大鼠的肾脏结构,血清尿酸、肌酐、尿素氮,大鼠尿α1微球蛋白、β2微球蛋白无明显影响,头孢替安钠500 mg·kg-1·d-1+呋塞米15 mg·kg-1·d-1给药后引起大鼠尿β2微球蛋白显著上升(P<0.05),血清尿酸显著下降(P<0.05)。结论:短期使用头孢替安钠对大鼠的肾功能及肾脏结构无明显影响,而头孢替安钠+呋塞米对大鼠尿β2微球蛋白及血清尿酸有一定影响。     

依那普利对环孢霉素相关性高血压的临床疗效及肾毒性的防护

目的:对11例肾移植术后患者合并应用CsA和依那普利,分別在合并用药前、合用7天后、停药7天后测定患者的血压、血清肌酐、尿素氮、CsA血药浓度。结果:患者合并用药前后的血清肌酐、尿素氮、CsA血浓度经统计学t检验无显著性差异,合并用药后血压较合并用前有显著下降(收缩压降低P<0.01,舒张压降低P<0.05)。结论:①依那普利与CsA合并用药时能对抗CsA相关性高血压,②对患者的肾功能无不良影响且具有一定的CsA肾毒性的防护作用,③基本不影响CsA的体内代谢。     

万古霉素对老年人肾功能的影响

目的：观察万古霉素对老年人肾功能的影响。方法：25例老年严重感染患者，每天予万古霉素0.5-2.0g，分1－2次iv gtt，平均疗程9d，治疗前后观察血清肌酐，血尿素氮，尿酸和内生肌酐清除率的变化。结果：24例患者在应用万古霉素前后血清肌酐，血尿素氮，尿酸，内生肌酐清除率的变化无显著性差异（P＞0．05），仅1例患者出现急性肾功能衰竭。结论：老年人应用万古霉素大多数是安全的，应根据内生肌酐清除率调整用药剂量，进行血药浓度监测，谨慎与袢利尿剂合用。     

64例老年患者万古霉素血药浓度监测结果分析

目的:通过分析64例老年肺部感染患者万古霉素血药浓度的监测结果,为临床合理用药提供参考.方法:采用荧光偏振免疫法测定万古霉素的血药浓度,对64例157例次血药浓度监测结果进行比较分析.结果:患者万古霉素血清峰浓度和谷浓度均在治疗窗范围内的仅占40% 左右,而谷浓度高于正常范围及峰浓度低于正常范围的约占50% ;首剂饱和方案组与首剂未饱和方案组中血清峰浓度比较有显著性差异,而谷浓度无显著性差异;肾功能正常组患者用药前、后内生肌酐清除率有显著性差异,尿素氮无显著性差异,而肾功能损害组患者用药前、后尿素氮及内生肌酐清除率均无显著性差异;近45% 的患者给药方案为500 mg,每日2~3 次,约75% 的患者未能达到有效峰浓度,约60% 的患者谷浓度超过正常水平.结论:老年感染患者使用万古霉素个体差异很大且多数患者伴有肾功能轻中度损害,应尽量给予首剂饱和方案并对其进行血药浓度监测,以利于实现个体化给药,进而提高该药应用的有效性和安全性.     

3种 头孢菌素对肾功能及环孢素血浓度的影响

５１例肾移植术后患者中随机分组，考查３种新头孢菌素分别与环孢素合并使用时对肾功能及环孢素全血药浓浓度的影响，在合并用头孢菌素前，合并用药７ｄ，停药后７ｄ测定患者的血清肌酐、尿素氮和环孢素全血药物浓度。     

肾移植患者环孢素A血药浓度与胱抑素C的相关性分析

目的:研究肾移植患者术后不同时期的环孢素A(CsA)血药浓度与血清胱抑素C(CysC)和血清肌酐(Scr)的相关性。方法:118例肾移植患者术后肾功能稳定(肌酐清除率>40 ml/min),其中男性60例,女性58例,共监测307例次。术后同时监测CsA血药浓度、CysC值和Scr。结果:随着术后时间的延长,CsA血药浓度呈逐渐下降趋势,CysC的均值高于正常参考范围,而Scr值均在正常参考范围内。术后不同时间段组、不同药物浓度组的CsA血药浓度与CysC和Scr均无显著相关性。结论:肾移植术后CsA血药浓度的高低,不影响CysC、Scr对移植肾功能的评价。     

16岁以下少年肾移植受者术后环孢素用药分析

对14例16岁以下肾移植受者术后2周内环孢素用药进行回顾性分析，结果在术后2周内所有受者的移植肾功能均恢复良好。环孢素的平均给药剂量为每天5．2±1.3mg／kg，环孢素血药浓度为160.37±60.71μg／L，环孢素浓度与剂量的比值为31.3±10．1，血尿素氮水平为17.6±6．1mmol／L，血清肌酐水平为210±102μmol／L。结果表明，少年肾移植患者术后环孢素服用剂量无需减量。     

197例肾移植患者环孢素A血药浓度监测数据分析

目的探讨肾移植患者环孢素A(CsA)血药浓度与效应关系,定性分析影响CsA血药浓度的各种因素.方法收集中山大学附属第一医院1999～2001年197例肾移植患者服用CsA 3d以上血药浓度达稳态后谷浓度数据,并作回顾性分析.结果 CsA血药浓度300～400ng/ml组的平均肌酐清除率与100～300ng/ml组有显著性差异(P<0.05).患者性别、年龄、体质量对CsA血药浓度有影响.结论不能单纯依赖血清肌酐浓度判断治疗效果,肾移植术后第1m,CsA血药浓度不宜低于300ng/ml,以免影响疗效.     

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。     

肾移植术后氨苄青霉素,诺氟沙星与环孢菌素的相互作用

对71例肾移植术后患者进行了氨苄青霉素与环孢菌素的相互作用研究。患者在开始服用氨苄青霉素之前、之中、之后的肾功能以及环孢菌素全血浓度测定结果表明,三项指标均无显著改变。另一组肾移植术后患者37例进行的诺氟沙星与环孢菌素相互作用研究,结果与氨苄青霉素的相互作用类似。提示氨苄青霉素、诺氟沙星可安全地与环孢菌素合用,而不影响肾功能。     

万古霉素对老年患者肾毒性的观察及血药浓度监测的意义

目的 探讨老年患者使用万古霉素治疗过程中进行肾毒性观察及血药浓度监测的意义。方法 对69例明确有金黄色葡萄球菌感染的老年住院患者予万古霉素500mg或去甲万古霉素400mg静滴，每8小时1次，平均疗程11d，观察用药前后肾功能指标的变化。31例患者在药物治疗过程中监测万古霉素血药浓度，根据检查结果调整治疗方案。结果 65例老年患者在应用万古霉素前后血清肌酐、血尿素氮、内生肌酐清除率的变化差异无统计学意义（P〉0．05）。结论 老年患者应用万古霉素大多数是安全的，根据内生肌酐清除率调整用药剂量及（或）进行血药浓度监测，进行个体化给药，可以提高该药应用的安全性和有效性。     

硫酸依替米星氯化钠注射液致肾损害

患者,男性,57岁,因腹膜后纤维化、双肾积水、泌尿系感染等症,给予硫酸依替米星氯化钠注射液0.3 g静脉滴注,每天1次,连续用药9d后,尿素氮由6.74 mmol·L-1上升至9.85 mmol·L-1,血清肌酐由103.0μmol·L-1升至373.9 μmol·L-1.停药6d后尿素氮降至5.11 mmol·L-1,血清肌酐降至122.1 μmol·L-1.随后的20多天里,仍按上述方案间断使用该药,用药过程中尿素氮及血清肌酐随用药或停药而上升或下降.在停药2周并针对原发病治疗后尿素氮恢复至2.94 mmol·L-1,肌酐恢复至76.0μmol·L-1.调整给药方案为硫酸依替米星氯化钠注射液,静脉滴注,0.15 g,每天2次,连续使用6d,尿素氮及血清肌酐未见明显升高.     

Effect of itraconazole on the concentrations of tacrolimus and cyclosporine in the blood of patients receiving allogeneic hematopoietic stem cell transplants

Purpose

The purpose of this study was to investigate the interactions of itraconazole (ITCZ) with orally administered calcineurin inhibitors (CNIs) in Japanese allogeneic hematopoietic stem cell transplant (HSCT) recipients.

Methods

Sixteen HSCT patients (8 patients each receiving tacrolimus or cyclosporine) were enrolled. An ITCZ oral solution was administered from day 30 after the initiation of ITCZ administration as a loading dose. Before the co-administration of ITCZ and CNI and 1 week daily thereafter, whole blood ITCZ and CNI (tacrolimus or cyclosporine) concentrations were measured in samples taken just before (C_0h) and 2 h (C_2h) after CNI administration.

Results

The median dose-adjusted C_0h values of tacrolimus and cyclosporine on day 7 after the start of ITCZ co-administration were 5.6- and 2.7-fold higher, respectively, than the corresponding values obtained before the initiation of ITCZ treatment. On day 7 after ITCZ treatment, the mean single dosages of tacrolimus and cyclosporine were reduced to 33.7 and 66.5 % of the dosages before ITCZ co-administration, respectively, to adjust the CNI target concentration. Although ITCZ co-administration did not alter the dose-adjusted C_0h values of tacrolimus in a patient with a CYP3A5*1/*1 allele, it did change this value of tacrolimus in patients with CYP3A5*3 alleles. However, in patients receiving cyclosporine, no such tendency was observed.

Conclusion

The magnitude of the interaction between orally administered tacrolimus and ITCZ was significantly greater than that between cyclosporine and ITCZ. Prospective analysis of the CYP3A5 polymorphism may be important to ensure safe and reliable immunosuppressive therapy with tacrolimus in patients treated with ITCZ.     

Ciclosporin metabolite pattern in blood and urine of liver graft recipients

Blood ciclosporin (Cs) metabolite pattern in 58 liver grafted patients was routinely monitored by HPLC from the first Cs dose after transplantation until discharge from hospital. Eighteen patients with normal kidney function were allocated to Group I and 14 patients in Group II suffered Cs nephrotoxicity during their clinical course. There were no significant differences between both groups in blood Cs level, kidney function before transplantation, liver function or co-administration of other potentially nephrotoxic drugs. A correlation matrix involving both groups showed a significant correlation between the blood concentration of metabolite M1c9 and serum creatinine and urea, and an inverse correlation with creatinine clearance. During a nephrotoxic episode the blood concentrations of metabolites M1c9 and M1A were significantly elevated in patients in Group II. Analysis of the time course revealed significantly higher blood levels of M19 and M1c9 in Group II patients compared with those in Group I for the first 10 days after transplantation. Serum creatinine and urea concentrations remained significantly elevated, the creatinine clearance being significantly reduced throughout the period of observation. The elevated blood concentrations of ciclosporin metabolites M1c9 and M19 during nephrotoxic episodes suggest that these metabolites are associated with ciclosporin nephrotoxicity. It could not be decided if the elevated metabolite concentrations were the result of and/or the reason for impaired kidney function.     

The safety of cefuroxime and gentamicin in patients with reduced renal function

Summary

The glomerular and tubular function of 7 patients with a spectrum of renal impairment was measured before, during and after 4-days' treatment with cefuroxime and gentamicin. Neither the mean plasma urea nor creatinine concentrations of the group increased after combined treatment, nor was the excretion of cefuroxime slowed. The ability to acidify and to concentrate the urine did not change. In only 1 patient did plasma creatinine increase and GFR fall. This patient had an unexpectedly high plasma gentamicin concentration and was taking frusemide. However, an eighth patient with acute renal failure caused by bacteraemic shock rapidly recovered renal function while being treated with cefuroxime and gentamicin for 15 days after large doses of frusemide intravenously. This limited study suggests that the useful combination of cefuroxime and gentamicin need not be denied to patients with reduced renal function, but emphasizes that the plasma gentamicin concentration must always be monitored.     

输尿管镜术治疗婴幼儿急性梗阻性双侧输尿管结石的评价

目的：探讨输尿管镜腔内治疗婴幼儿急性梗阻性双侧输尿管结石的有效性及安全性。方法回顾性分析2011年9月至2013年9月新疆维吾尔自治区人民医院收治的16例双侧输尿管结石婴幼儿,行一期U-100激光碎石或逆行置管引流治疗。输尿管上段结石9侧,输尿管下段结石23侧,合并肾结石5例,结石直径6～14 mm,平均（7．4±1．9） mm。术前检查血尿素氮25～49 mmol/L,血肌酐270～835μmol/L,血尿酸623．7～1640．5μmol/L,血钾4．5～6．8 mmol/L。观察手术前后尿量、血尿素氮、血肌酐、血尿酸、血钾变化。结果输尿管镜下U-100一期双侧输尿管成功碎石8例,7例逆行置入输尿管支架管引流,双侧置管4例,单侧置管3例,1例逆行置管失败改开放手术。6例二期手术碎石,治愈15例,死亡1例。平均手术时间（45±7）min,平均住院时间（9．1±2．3）d。术后第3天血尿素氮1．9～5．9 mmol/L,血肌酐45～76μmol/L,血尿酸125．6～296．7μmol/L,血钾3．2～4．8 mmol/L。结论输尿管镜联合U-100激光碎石或逆行置入输尿管支架管引流治疗婴幼儿急性梗阻性双侧输尿管结石临床有效,创伤小,治疗效果理想。     

Kinetics of drug action in disease states. XXXVI: Effect of cyclosporine on the pharmacodynamics and pharmacokinetics of a barbiturate (heptabarbital) in rats

Pretreatment with cyclosporine reportedly prolongs the effect of certain general anesthetics in humans and the sleeping time of mice after pentobarbital administration. This investigation was designed to determine the mechanism(s) of the cyclosporine-barbiturate interaction. Adult female Wistar rats received cyclosporine (50 mg/kg im) or saline solution daily for 3 days. On the third day, they were injected with heptabarbital (45 mg/kg iv). Other cyclosporine-treated and control groups were infused with heptabarbital until they lost their righting reflex. Treatment for 3 d with cyclosporine was associated with decreased rectal temperature, decreased magnesium concentrations in serum and CSF, increased serum creatinine and urea nitrogen concentrations, elevated serum aspartate aminotransferase activity and total bilirubin concentration, decreased serum total protein concentration, and increased hematocrit. These physiologic changes are consistent with the clinically observed hypomagnesemia, nephrotoxicity, and hepatotoxicity in patients treated with cyclosporine. Control rats slept for 90 +/- 14 min (mean +/- SD, n = 9) after heptabarbital injection, whereas cyclosporine-pretreated rats slept for 154 +/- 22 min. Compared with controls, cyclosporine-pretreated rats awoke (after heptabarbital injection) and went to sleep (after heptabarbital infusion) with significantly lower barbiturate concentrations in serum and CSF. Pretreatment with a single 60-mg/kg im dose of cyclosporine 2 h before heptabarbital infusion caused no significant biochemical changes approximately 160 min later, except for elevated serum aspartate aminotransferase (which occurred also after injection of the surfactant-containing vehicle) and serum bilirubin. Again, heptabarbital concentrations at onset of sleep (loss of righting reflex) in serum, brain, and CSF of cyclosporine-treated rats were significantly lower than in saline-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)