盐酸黄连素对肾移植受者环孢素A增效作用的临床药代动力学研究

目的研究盐酸黄连素对肾移植受者使用环孢素A增效作用的体内动力学过程.方法选择肾移植术后1个月以内、连续服用环孢素A 2周、肝肾功能稳定的患者6名,环孢素A剂量6mg.kg-1·d-1,用FPIA方法(单抗)检测合用黄连素前后各时间点环孢素A全血浓度.结果单服环孢素A的主要药代动力学参数分别为tmax(h)1.33±0.52,Cmax(μg·L-1)1224.75±296 20,Cmin(μg·L-1)173.95±78.71,t1/2(h)2.62±1.00,AUC μg·h·L-14681.34±1300.45,CL/F(L·h-1)35±15;与黄连素合用的主要药代动力学参数为tmax(h)3.00±1.26,Cmax(μg·L-1)1050.10±290.86,Cmin(μg·L-1)321.31±161.29,t1/2(h)5.33±2.60,AUCμg·h·L-16265.71±1 871.33,CL/F(L·     

肾移植病人口服环孢素的药代动力学

本文用HPLC法测定环孢素的全血浓度,对8例异体肾移植病人口服环孢素后的药代动力学特性进行研究。病人在肾移植后用环孢素的时间为47天到11个月,平均给药剂量为8.26±1.41 mg/kg·d(5.88～10.0mg/kg·d),每12h一次。病人常规监测血样本300余次。测得病人的环孢素药代动力学参数:峰浓度(Cmax)664.9±87.5 ng/ml,达峰时间(Tmax)3.27±1.07h;t¹/₂β13.53h(6.13～44.3h)。     

肾移植术后患者口服环孢素的药代动力学研究

环孢素A(CsA)是一种高效能的免疫抑制剂，广泛应用于肾脏、肝脏等器官移植及其他疾病的治疗。但由于其不良反应多，治疗窗较窄，个体差异较大，因此根据血药浓度监测情况及时调整用药剂量日益受到临床重视。在器官移植术后CsA的剂量调整中，(CsA谷值(C0值)是一个常用的指标。     

地尔硫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尔硫对２６例肾移植受者环孢素Ａ血药浓度的影响，同时以不用地尔硫的２１例肾移植受者为对照。结果表明：地尔硫组环孢素Ａ血药浓度明显升高，而环孢素Ａ的用量明显较对照组减少，术后１２个月中用地尔硫组环孢素Ａ用量每例平均较对照组少１４．８７０ｇ。结果提示：地尔硫与环孢素Ａ合用，可明显减少肾移植受者环孢素Ａ的用量。     

氯沙坦对家兔环孢素A药代动力学影响的研究

目的研究氯沙坦对家兔环孢素A（CsA）药代动力学的影响。方法采用荧光偏振免疫法（FPIA法）测定6只家兔合用氯沙坦前后CsA的血药浓度,并对2组（单用CsA组和合用氯沙坦组）药代动力学参数进行分析。结果合用氯沙坦组的CsA峰浓度（Cmax）、曲线下面积（AUCν0-24）均显著升高（P〈0．01）,血浆清除率（cL）及表观分布容积（V）均显著降低（P〈0．05或P〈0．01）,其余药动学参数无显著性变化（P〉0．05）。结论合用氯沙坦可升高CsA的血药浓度,临床上其与CsA合用需监测CsA的血药浓度,保证治疗的安全有效。     

氯沙坦对兔体内环孢素A药代动力学的影响

目的研究氯沙坦对兔体内环孢素A（CsA）药代动力学的影响。方法采用荧光偏振免疫法测定6只家兔单用及合用氯沙坦后CsA的血药浓度,并对两组动物药代动力学参数进行统计学分析。结果合用氯沙坦后CsA的峰浓度（Cmax）、药时曲线下面积（AUC）显著升高,清除率（CL）及表观分布容积（V）显著降低,其余药代动力学参数无显著性变化。结论氯沙坦可升高CsA的血药浓度,临床上两药合用必须监测CsA的血药浓度,保证治疗安全有效。     

氯沙坦对家兔环孢素A药代动力学影响的研究

目的 研究氯沙坦对家兔环孢素A(CsA)药代动力学的影响.方法 采用荧光偏振免疫法(FPIA法)测定6只家兔合用氯沙坦前后CsA的血药浓度,并对2组(单用CsA组和合用氯沙坦组)药代动力学参数进行分析.结果 合用氯沙坦组的CsA峰浓度(Cmax)、曲线下面积(AUC0→24)均显著升高(P<0.01),血浆清除率(CL)及表观分布容积(V)均显著降低(P<0.05或P<0.01),其余药动学参数无显著性变化(P＞0.05).结论 合用氯沙坦可升高CsA的血药浓度,临床上其与CsA合用需监测CsA的血药浓度,保证治疗的安全有效.     

肾移植患者术后口服环孢素A的群体药动学研究

目的考察肾移植患者术后口服环孢素A的群体药动学(population pharmacokinetics,PPK)模型,为临床个体化用药提供参考。方法回顾性收集空军总医院62名肾移植术后口服环孢素A患者常规血药浓度监测数据160个。用NONMEM法建立PPK模型,并考察性别、年龄、体重、术后时间、肝肾功能及联合用药等固定效应对药动学参数的影响。结果患者体重(WT)、红细胞压积(HCT)、总胆红素水平(TBIL)对环孢素A体内清除率有影响。最终模型公式为:CL/F=30.5×[1+0.0105×(WT-61.36)]×[1-1.15×(HCT-0.289)]×[1-0.0125×(TBIL-9.26)](L.h-1);Vd/F=3.85×WT(L);Ka=1.28(h-1)。CL/F的个体间变异为10.9%。用Bootstrap法对模型进行内部验证,结果显示模型稳定可靠。结论用NONMEM软件拟合可获得肾移植患者术后口服环孢素A的PPK最终模型,该模型可为临床合理使用环孢素A提供参考依据。     

联苯双酯对兔体内环孢素A药代动力学影响的实验及临床观察

目的:考察联苯双酯(BFD)与环孢素A(CsA)在兔体内并用后,对CsA动力学过程的影响.方法:用高效液相色谱法测定6只兔在单用CsA和并用BFD后CsA的血药浓度,并进行动力学参数的计算与比较.结果:CsA与BFD并用后,CsA在兔体内的血浓度普遍降低,表观分布容积及清除率显著增大(0.05＞P＞0.01),AUC明显小于单用CsA(0.05＞P＞0.01)时的AUC,其余的参数无统计学差异.通过临床观察,验证了肾移植患者在同时服用CsA和BFD后造成体内CsA全血药物浓度降低,与兔实验结果一致.结论:BFD可明显降低CsA的血药浓度,不宜与CsA联用.     

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。     

来曲唑在大鼠体内药代动力学的性别差异(英文)

目的:研究来曲唑(Letr)药动学性别差异性。方法:ig Letr 2mg/kg后,测定在雄、雌性大鼠血浆、组织中浓度及粪、尿中回收率。结果:ig Letr 6 h以后,雄鼠中血药浓度显著低于雌鼠,如给药24,36,48和72h,雌鼠血药浓度分别为雄鼠的3.3,5.6,10.5和7.4倍。雄鼠AUC也仅为雌鼠的1/3,其半衰期分别为10.5和40.4h。120h内,雌鼠尿和粪中排泄分数分别为5.78％±1.40％和6.61％±1.10％,而雄鼠仅分别为1.30％±0.59％和0.87％±0.31％;给药后24h,雌鼠组织中药物浓度显著高于雄鼠。结论:Letr在大鼠体内的药动学存在较大的性别差异。     

Bayesian estimation of cyclosporin exposure for routine therapeutic drug monitoring in kidney transplant patients

AIMS: AUC-based monitoring of cyclosporin A (CsA) is useful to optimize dose adaptation in difficult cases. We developed a population pharmacokinetic model to describe dose-exposure relationships for CsA in renal transplant patients and applied it to the Bayesian estimation of AUCs using three blood concentrations. METHODS: A total of 84 renal graft recipients treated with CsA microemulsion were included in this study. Population pharmacokinetic analysis was conducted using NONMEM. A two-compartment model with zero-order absorption and a lag time best described the data. Bayesian estimation was based on CsA blood concentrations measured before dosing and 1 h and 2 h post dose. Predictive performance was evaluated using a cross-validation approach. Estimated AUCs were compared with AUCs calculated by the trapezoidal method. The Bayesian approach was also applied to an independent group of eight patients exhibiting unusual pharmacokinetic profiles. RESULTS: Mean population pharmacokinetic parameters were apparent clearance 30 l h(-1), apparent volume of distribution 79.8 l, duration of absorption 52 min, absorption lag time 7 min. No significant relationships were found between any of the pharmacokinetic parameters and individual characteristics. A good correlation was obtained between Bayesian-estimated and experimental AUCs, with a mean prediction error of 2.8% (95% CI [-0.6, 6.2]) and an accuracy of 13.1% (95% CI [7.5, 17.2]). A good correlation was also obtained in the eight patients with unusual pharmacokinetic profiles (r(2) = 0.96, P < 0.01). CONCLUSIONS: Our Bayesian approach enabled a good estimation of CsA exposure in a population of patients with variable pharmacokinetic profiles, showing its usefulness for routine AUC-based therapeutic drug monitoring.     

肾移植后监测肿瘤坏死因子与环孢素A血药浓度的临床意义

目的研究肾移植术后患者肿瘤坏死因子(TNF)与全血环孢素A(CsA)浓度的临床意义。方法采用放射免疫法测定血清和尿TNF,FPIA法测定CsA全血浓度。结果急性排斥组患者血、尿TNF(1.03±0.26ng/L,0.44±0.36ng/L)明显高于肾功能稳定组(0.86±0.21ng/L ,0.34±0.29ng/L),并且可早于血肌酐升高1～3d。而CsA肾中毒组的血、尿TNF(0.91±0.22ng/L、0 40±0.27ng/L)与肾功能稳定组无明显差别。CsA血药浓度在急性排斥反应组明显降低 ,而CsA肾中毒组显著升高。结论TNF和CsA血药浓度测定有助于鉴别急性排斥反应和CsA肾中毒 ,具有重要的临床意义     

Pharmacokinetics of oral cyclosporin A in diabetic children and adolescents

Summary Cyclosporin A (CsA) pharmacokinetics was studied in 19 diabetic children (mean age: 10.6 y). They were divided into prepubertal (I) and pubertal (II) groups according to plasma oestradiol or testosterone concentrations. The kinetic study was performed after a 72 h wash out period and a single oral dose of 7.5 mg/kg CsA. CsA in blood was measured by HPLC. The kinetic parameters: C_max, t_max, t_1/2, AUC, CL/f, Vz/f and tss were calculated.No significant difference was found between the two groups. A significant negative correlation was found between V_z and both total cholesterol (r=0.46), VLDL+LDL–cholesterol (r=–0.49) and VLDL+LDL–phospholipids (r=–0.58). CsA kinetics at steady-state were simulated by superimposition of single dose kinetics derived from each single dose. Measured steady-state blood concentrations were correlated (r=0.80) with the values predicted by the simulation. The results suggest that CsA adjustment dosage of the CsA may be performed after a single oral dose using blood levels measured by HPLC. This procedure requires validation in further studies.     

肝移植术后患者环孢素A药物动力学与红细胞膜脂流动性的动态观察

目的探讨肝移植术后患者细胞膜脂流动性与环孢素A(CsA)药物动力学相关性,减少药物引起的不良反应.方法采用FPLA法测定CsA全血药物浓度,DPH荧光探针法测定红细胞膜脂流动性.结果红细胞膜脂流动性的动态改变与血中CsA药物浓度的变化呈负相关.结论CsA可使细胞膜脂流动性降低,长期低水平的膜脂流动性是导致肝损害的病理学基础.     

大鼠口服尼莫地平吸收动力学性别差异研究

目的 :研究大鼠ig尼莫地平 (NMD)后体内药物动力学是否存在性别差异 ,并考察合用红霉素(Ery)后血浆中NMD变化。方法 :雌性和雄性大鼠单独igNMD或与Ery合用后 ,用HPLC法测定血浆中NMD的浓度。结果 :大鼠ig给药NMD(2 0mg·kg-1) ,雌鼠血浆中的NMD浓度显著高于雄鼠 (P <0 .0 5 ) ,其AUC值是雄鼠的 4 .4倍。合用Ery后 ,与单用比较 ,无论是雄鼠 ,还是雌鼠 ,血浆中NMD浓度显著升高 ,AUC值分别提高了 2 .0和 1.6倍。合用Ery ,NMD的性别差异仍然存在。雌鼠的浓度仍然高于雄鼠 ,AUC值是雄鼠的 3.4倍。结论 :NMD在大鼠体内口服吸收动力学存在性别差异 ,并且红霉素可以提高NMD在血浆中的浓度。     

Alterations in cyclosporin A pharmacokinetics and metabolism during treatment with St John's wort in renal transplant patients

AIM: This study investigated the effects of St John's wort extract (SJW) on the pharmacokinetics and metabolism of the immunosuppressant cyclosporin A (CSA). METHODS: In an open-label study, 11 renal transplant patients received 600 mg SJW extract daily for 14 days in addition to their regular regimen of CSA. Blood concentrations of CSA and its metabolites AM1, AM1C, AM9, AM19, and AM4N were measured by HPLC. RESULTS: After 2 weeks of SJW coadministration, dose-corrected AUC0-12, Cmax and Ctrough values for CSA decreased significantly by 46%[geometric mean ratio baseline/SJW (95% CI): 1.83 (1.63-2.05)], 42%[1.72 (1.42-2.08)], and 41%[1.70 (1.17-2.47)], respectively. CSA doses were increased from a median of 2.7 mg day(-1) kg(-1) at baseline to 4.2 mg day(-1) kg(-1) at day 15, with the first dose adjustment required only 3 days after initiation of SJW treatment. Additionally, the metabolite pattern of CSA was substantially altered during SJW treatment. Whereas dose-corrected AUC values for AM1, AM1c and AM4N significantly decreased by 59%, 61%, and 23% compared with baseline, AUC values for AM9 and AM19 were unchanged. Following the increase in CSA dose, observed AUC and Cmax values for AM9, AM19, and AM4N increased by 20-51% and 43-90%, respectively. CONCLUSION: Administration of SJW extract to patients receiving CSA treatment resulted in a rapid and significant reduction of plasma CSA concentrations. Additionally, the substantial alterations in CSA metabolite kinetics observed may affect the toxicity profile of the drug.     

Autonomic modulation analysis in active and sedentary kidney transplanted recipients

Modulation of the autonomic nervous system on heart rate can be compromised in chronic kidney disease and may result in changes in the frequency and duration of the cardiac cycle. The aim of this study was to evaluate autonomic modulation in active and sedentary renal transplant recipients. Twenty renal‐transplanted individuals were analyzed at the Centro de Prevenção de Doenças Renais (Kidney Disease Education Centre), in the academic hospital of Universidade Federal do Maranhão, and were divided into the active group (AG) and the sedentary group (SG). The AG comprised of six men and four women (age 43.10 ± 13.02) and was in regular concurrent training intervention for 8 weeks, while the SG was composed of three men and seven women (age 36.8 ± 9.26). Analysis of heart rate (HR) variability in time and frequency domain demonstrated that HR mean values in the SG and AG were 787.32 ± 79.60 and 870 ± 106.66 ms, respectively. Differences were observed in the time domain and frequency domain. The total index of low frequency and high frequency showed no differences between the SG and AG. Biochemical variables presented significantly lower levels after 8 weeks of training. Higher heart rate variability in the time domain and greater vagal modulation was observed in the AG. The AG ad greater vagal modulation when compared to the SG, with removal of the sympathetic and increased parasympathetic in the behaviour was confirmed by sympatho‐vagal balance. The AG also presented significant improvements in the frequency domain.