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1.
A number of classical pharmacokinetic studies have been conducted in transplant patients. However, they suffer from some limitations, for example, (1) the study design was limited to intense blood sampling in small groups of patients during a certain posttransplant period, (2) patient factors were evaluated one at a time to identify their association with the pharmacokinetic parameters, and (3) mean pharmacokinetic parameters often cannot be precisely estimated due to large intraindividual variability. Population pharmacokinetics provides a potential means of addressing these limitations and is a powerful tool to evaluate the magnitude and consistency of drug exposure. Population pharmacokinetic studies of cyclosporine focused solely on developing limited sampling strategies and Bayesian estimators to estimate drug exposure, have been summarized before, and are, therefore, not a subject of this review. The major focus of this review is to describe factors (demographic factors, hepatic and gastrointestinal functions, drug–drug interactions, genetic polymorphisms of drug metabolizing enzymes and transporters) that have been identified to contribute to the large portion of observed variability in the pharmacokinetics of cyclosporine in transplant patients. This review summarizes and interprets the conclusions as well as the nonlinear mixed-effects modeling methodologies used in such studies. A highly diversified collection of structural models, variability models, and covariate submodels have been evaluated and validated using internal or external validation methods. This review also highlights areas where additional research is warranted to improve the models since a portion of model variability still remains unexplained. 相似文献
2.
目的:探讨肾移植患者全血他克莫司浓度的治疗窗及对血常规和肝肾功能的影响。方法:MEIA法监测全血他克莫司谷浓度。对近4年来390例次肾移植患者全血他克莫司浓度,及他克莫司对血常规和肝肾功能的影响进行分析。结果:390例次全血他克莫司浓度中377例次(80.8%)在3~15μg·L^-1的范围内。移植后6个月内,全血他克莫司浓度差异较大。随着移植时间延长,全血他克莫司浓度逐步降低。在治疗剂量内,他克莫司对肾移植受者的血常规和肝肾功能无明显影响。结论:全血他克莫司谷浓度的治疗窗:术后1~3月为5~15·L^-1,第4~6月为5~10·L^-1,〉6个月为3~10·L^-1。他克莫司对肾移植受者的血常规和肝肾功能无明显影响。 相似文献
3.
Cai J Huang Z Yang G Cheng K Ye Q Ming Y Zuo X Zhou P Yuan H 《Am J Cardiovasc Drugs》2011,11(6):401-409
Background
Hypertension, a major complication in kidney transplant recipients, is associated with premature death and graft loss. However, an optimal antihypertensive therapy for these patients has not been established [Chinese Clinical Trial Registry No. ChiCTR-TRC-10001071].Objective
The aim of the present study was to evaluate the effect of amlodipine and valsartan on BP control in renal transplant patients and to analyze the correlation between cytochrome P450 (CYP) 3A5 or multidrug resistance-1 gene (MDR1) genotype and the antihypertensive effect of these two regimens.Methods
150 renal transplant patients with stage 1 or 2 hypertension were enrolled in the trial. Patients were randomly assigned to amlodipine or valsartan. Metoprolol was added if BP was not under control after 4 weeks. BP and plasma levels of ciclosporin were monitored during the 24-week trial. CYP3A5 and MDR1 genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Results
The demographic features and baseline BP were similar between these two groups. During the 24-week trial, the reduction of systolic BP (SBP) was similar between the amlodipine and valsartan groups. However, the reduction of diastolic BP (DBP) was significantly greater in the amlodipine group compared with the valsartan group at 12, 16, and 24 weeks of treatment. The plasma level of ciclosporin at 2 hours of medication was significantly higher in the amlodipine group than in the valsartan group after 4 weeks of the trial. The reduction of DBP at 24 weeks was greater in the subjects with CYP3A5 *3/*3 variant than in those with CYP3A5*1/*1 variant (?13.5± 1.9mmHg vs ?8.7± 1.6mmHg, p<0.05).Conclusion
The present study demonstrated that amlodipine produced a greater reduction of DBP than valsartan, although both amlodipine and valsartan resulted in satisfactory control of BP in patients with renal transplantation. Administration of amlodipine significantly increased the plasma concentration of ciclosporin, and its effects on BP control and ciclosporin concentration may be associated with the CYP3A5 genotype in these subjects [Chinese Clinical Trial Registry No. ChiCTR-TRC-10001071]. 相似文献4.
5.
Dr. Kathleen M. Tornatore Pharm.D. Ms. Kristine A. Reed R.N. Dr. Rocco C. Venuto M.D. 《Pharmacotherapy》1993,13(5):481-486
Study Objective . To examine the comparative pharmacokinetics of long-term methylprednisolone therapy in black and white renal transplant recipients. Design . Comprehensive pharmacokinetic evaluations of patients who participated in our glucocorticoid-monitoring program. Setting . University-based renal transplantation clinic. Patients . Six white renal transplant recipients with stable renal function, sex-and (approximate) age-matched with six preselected black patients. Interventions . The daily oral methylprednisolone dose for each patient was administered intravenously, and serial plasma samples were obtained over 24 hours. Measurements and Main Results . Methylprednisolone was analyzed by high-performance liquid chromatography. The drug's pharmacokinetics in black and white patients, respectively, were as follows: mean clearance 234 ± 124 and 472 ± 180 ml/hr/kg (p<0.05); volume of distribution 0.3-2.0 and 0.8-2.0 L/kg; and elimination rate constant 0.13-0.41 and 0.27-0.42 hour−1 (p<0.06). No statistical difference was noted in the last two parameters. The mean half-life of 3.4 ± 1.4 hours in black patients compared with 2.1 ± 0.3 hours in white patients approached statistical significance (p<0.08). Conclusions . These preliminary observations suggest that the disposition of methylprednisolone differs between black and white renal transplant recipients. The current method of prescribing glucocorticoids employs a fixed-dose regimen that does not take these possible interracial differences into consideration. Incorporating the differences may allow for more individualized dosing and more efficacious use of the agent in this patient population. 相似文献
6.
68例肾移植受者环孢素血药浓度监测 总被引:3,自引:2,他引:1
目的:分析环孢素血药浓度与剂量、疗效的关系。方法:以高效液相色谱法对68例肾移植受者进行556次环孢素血药浓度监测。结果:肾移植术后不同时期环孢素全血谷浓度分别为289.3±126.0(1个月),229.2±101.6(2个月),199.1±108.7(3个月),144.9±53.5(4~12个月),135.6±51.9ng·ml~(-1)(>12个月),500例次肝肾功能正常,占89.9%,53例次不正常,占9.5%,3例次出现慢性排斥,经应用激素冲击疗法和增加环孢素用量得以纠正。结论:环孢素血药浓度监测具有重要的临床意义。 相似文献
7.
目的:分析肾移植患者术后环孢素A(CsA)血药浓度与剂量、疗效的关系。方法:采用荧光偏振免疫法(FPIA)对70例肾移植患者进行251次CsA全血药物浓度测定。结果:肾移植术后不同时间段CsA血药谷浓度0~3个月时为(336.99±224.89)ng/mL,3~6个月为(252.07±113.71)ng/mL,6~12个月为(195.83±105.11)ng/mL,1~2年为(179.64±85.48)ng/mL,2年以上则为(144.95±55.68)ng/mL。结论:CsA药物浓度的跟踪检测对观察肾移植术后的排异反应、减少药物不良反应具有重要的临床意义。 相似文献
8.
Dr. Erika J. Wolfe Pharm.D. Dr. Vandana Mathur M.D. Dr. Stephen Tomlanovich M.D. Dr. Don Jung Ph.D. Dr. Rodney Wong Ph.D. Dr. Kay Griffy Pharm.D. Dr. Francesca T. Aweeka Pharm.D. 《Pharmacotherapy》1997,17(3):591-598
Study Objectives . To evaluate the pharmacokinetics of mycophenolic acid and its glucuronide metabolite alone and in the presence of ganciclovir, and to determine the pharmacokinetics of ganciclovir alone and in combination with mycophenolate mofetil. Design . Randomized, open-label, three-way crossover study. Patients . Twelve kidney transplant recipients. Interventions . Mycophenolate mofetil 1500 mg orally and ganciclovir 5 mg/kg intravenously were each given alone and in combination with at least a 1-week washout period between treatment arms. Measurements and Main Results . Blood samples were obtained to measure mycophenolic acid and ganciclovir by high-performance liquid chromatography. Mean (± SD) oral plasma clearance for mycophenolic acid alone and with ganciclovir was 3.11 ± 0.72 and 3.19 ± 0.72 ml/min/kg (p=0.64). The overall disposition of the major metabolite, MPA-glucuronide, was unchanged, with approximately 70% of the administered dose eliminated as the glucuronide conjugate for both arms of the study. Mean ganciclovir serum clearance was 1.80 ± 0.58 ml/min/kg for ganciclovir and 1.70 ± 0.55 ml/min/kg for ganciclovir plus mycophenolate mofetil (p=0.11; 10 patients). Renal clearance of ganciclovir was decreased when the drugs were administered in combination, 1.43 ± 0.54 (ganciclovir) and 1.26 ± 0.44 (both drugs) ml/min/kg (p=0.02; 10 patients). Conclusion . The single-dose pharmacokinetics of mycophenolic acid and its glucuronide metabolite were unchanged by the addition of ganciclovir. Total serum clearance of ganciclovir was unchanged by the addition of mycophenolate mofetil, however, renal clearance was slightly decreased. 相似文献
9.
目的:研究造血干细胞移植术后患者的环孢素A(CsA)血药浓度与各生化指标以及合并使用药物的相关性。方法:记录本院造血干细胞移植术后静脉注射CsA和口服CsA患者的血药浓度值、相应生化检验值及喹诺酮类抗菌药、三唑类抗真菌药、护肝类药、糖皮质激素类药、质子泵抑制剂、胃肠动力药的使用数据,应用SPSS13.0统计软件对数据进行线性回归分析。结果:患者静脉注射CsA单位剂量后血药浓度与总胆红素(TBIL)、γ-谷氨酰转肽酶(γ-GTP)、天门冬酸氨基转移酶(AST)及喹诺酮类药之间的相关性具有统计学意义;口服CsA单位剂量后血药浓度与直接胆红素(DBIL)、尿酸(UA)、尿素氮(BUN)、三唑类抗真菌药及糖皮质激素类药之间的相关性具有统计学意义。结论:CsA血药浓度受患者自身体内一些因素以及合用药物影响。 相似文献
10.
Safety and Feasibility of Outpatient Rabbit Antithymocyte Globulin Induction Therapy Administration in Kidney Transplant Recipients
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Alexandra N. Varga David Johnson Deirdre L. Sawinski Mary Ann Lim Roy D. Bloom Peter L. Abt Simin Goral Melissa Bleicher Matthew H. Levine Ali Naji Susanna Nazarian Paige Porrett Jennifer Trofe‐Clark 《Pharmacotherapy》2018,38(6):620-627
11.
肾移植患者口服环孢素A的血药浓度监测分析 总被引:5,自引:0,他引:5
目的动态监测分析肾移植患者环孢素A血药浓度,指导临床合理用药。方法应用荧光偏振免疫分析法测定52例肾移植患者环孢素A血药浓度。结果在52例肾移植患者252次环孢素A血药浓度监测中,有195次(77.3%)达到有效血药浓度(100~400 ng.mL-1),其平均浓度为(207.17±62.52)ng.mL-1,有46次(18.3%)低于有效血药浓度(Cmin<100 ng.mL-1),其平均浓度为(72.78±16.92)ng.mL-1,有11次(4.4%)超过有效血药浓度(>400 ng.mL-1),其平均浓度为(581.76±141.55)ng.mL-1。结论环孢素A用药具有个体化的特点,动态监测其血药浓度对于肾移植患者安全、有效用药非常重要。 相似文献
12.
Dr Ashley Irish 《Am J Cardiovasc Drugs》2004,4(3):139-149
Renal transplantation improves survival and quality of life for patients with end-stage renal disease (ESRD). Improvements in immunosuppressive therapy have reduced early allograft loss due to acute rejection to very low levels. Early allograft loss, due to acute thrombotic complications, remains a constant and proportionally increasing complication of renal transplantation. Identifying risk factor(s) for thrombosis amenable to preventive strategies has been elusive. Epidemiological studies have attempted to define risk in terms of modifiable (drugs, dialysis modality, surgical procedure) and non-modifiable (age, diabetes mellitus, vascular anomalies) factors, or identify changes in coagulation or fibrinolysis promoting a more thrombotic state. Most recently the evolution of thrombophilia research has established the potential for inherited hypercoagulability to predispose to acute allograft thrombosis. Inheritance of the factor V Leiden (FVL), prothrombin G20210A mutation, or the presence of antiphospholipid antibodies (APA) may increase the risk of renal allograft thrombosis approximately 3-fold in selected patients. Patients with ESRD due to systemic lupus erythematosus (SLE) appear at particularly high risk of thrombosis, especially if they have either APA or detectable beta(2)-glycoprotein-1. Data for other hypercoagulable states such as hyperhomocystinemia or the C677T polymorphism of the methylenetetrahydrofolate reductase gene are deficient. Patients with APA, FVL, or prothrombin G20210A mutation also appear to have greater graft loss due to vascular rejection, possibly reflecting immunological injury upon the vascular wall exacerbated or induced by the prothrombotic state. While substantial in vitro data suggest cyclosporine is prothrombotic, an independent clinical association with allograft thrombosis is unproven. Interventions to reduce thrombotic risk including heparin, warfarin, and aspirin have been evaluated in both selected high-risk groups (heparin and warfarin) and unselected populations (heparin and aspirin). In unselected patients at low clinical risk, aspirin (75-150 mg/day) with or without a short period of unfractionated heparin (5000U twice a day for 5 days) appears to reduce the risk of renal allograft thrombosis significantly with a low risk of bleeding, especially when compared with low molecular weight heparins which risk accumulation in renal failure. In high-risk groups (identified thrombophilic risk factor, previous thrombosis, or SLE) longer period of heparin, with or without aspirin and maintenance with warfarin, should be considered. Re-transplantation following graft loss due to vascular thrombosis can be undertaken with a low risk of recurrence. Further prospective studies evaluating both putative risk factors and intervention strategies are required to determine whether routine clinical screening for thrombophilic factors is justified. 相似文献
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14.
环孢素固体分散体大鼠体内药动学及相对生物利用度的初步研究 总被引:2,自引:1,他引:2
目的:研究环孢素的全血浓度测定方法;以市售新山地明(NeoralR)为参比制剂,研究自制环孢素固体分散体(CsASD)在大鼠体内的药动学和相对生物利用度.方法:两组SD雄性大鼠分别单剂量给予CsA-SD和NeoralR,按设计采集48 h内动态血标本,采用HPLC法测定血药浓度.应用3P87药动学程序对数据进行拟合计算药动学参数.结果:单次给药后Ne-oralR和CsA-SD的主要药动学参数Cmax分别为(4 029.7±405.8)ng·ml-1和(3 958±1 455)ng·ml-1,tmax分别为(1.54±0.57)h和(1.90±0.51)h,AUC0→48分别为(75 072±25 453)ng·h·ml-1和(84 861±26 392)ng·h·ml-1.统计分析结果显示,各主要药动学参数均无显著性差异.以NeoralR为参比制剂,单剂量给药时CsA-SD的相对生物利用度为113.04%.结论:环孢素固体分散体在大鼠体内显示与市售新山地明相近的生物利用度. 相似文献
15.
We attempted to characterize circadian variations in pharmacokinetic parameters of a new formulation of cyclosporine (CsA) in nine cardiac allograft recipients. A secondary objective was to determine the sampling time that correlated best with exposure of patients to the drug. This was a two-period study with each period lasting 12 hours. All patients received two equal doses of a new microemulsion of CsA 12 hours apart. Blood samples to measure drug levels were obtained at administration and 1, 2, 3, 4, 6, 9, and 12 hours after each dose. We found no statistically significant difference in pharmacokinetic parameters (areas under the curve, minimum blood concentration, oral clearance) measured during the day and during the night. However, maximum blood concentrations during the day were 30% higher than those at night (p<0.05). We found a good correlation between minimum concentrations in the morning and overall exposure of patients to CsA (r = 0.89). This new microemulsion appears to have few circadian variations of blood concentrations in cardiac transplant recipients. The clinical significance of higher maximum blood concentration during daytime remains to be elucidated. Our results support the most widely accepted method for monitoring CsA, which is based on minimum concentrations in the morning. 相似文献
16.
Natalia Korytowska Aleksandra Wyczakowska-Tomasik Leszek Pczek Joanna Giebutowicz 《Toxins》2021,13(8)
Acute kidney injury (AKI) is a significant risk factor for developing chronic kidney disease and progression to end-stage renal disease in elderly patients. AKI is also a relatively common complication after kidney transplantation (KTx) associated with graft failure. Since the lifespan of a transplanted kidney is limited, the risk of the loss/deterioration of graft function (DoGF) should be estimated to apply the preventive treatment. The collection of saliva and urine is more convenient than collecting blood and can be performed at home. The study aimed to verify whether non-invasive biomarkers, determined in saliva and urine, may be useful in the prediction of DoGF in kidney transplant recipients (KTRs) (n = 92). Salivary and serum toxins (p-cresol sulfate, pCS; indoxyl sulfate, IS) concentrations were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Urinary proteins, hemoglobin, and glucose were measured using a semi-quantitative strip test. Salivary IS (odds ratio (OR) = 1.19), and proteinuria (OR = 3.69) were demonstrated as independent factors for the prediction of DoGF. Satisfactory discriminatory power (area under the receiver operating characteristic curve (AUC) = 0.71 ± 0.07) and calibration of the model were obtained. The model showed that categories of the increasing probability of the risk of DoGF are associated with the decreased risk of graft survival. The non-invasive diagnostic biomarkers are a useful screening tool to identify high-risk patients for DoGF. 相似文献
17.
Development of a Predictive Model for Drug‐Related Problems in Kidney Transplant Recipients
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Kelly L. Covert Caitlin R. Mardis James N. Fleming Nicole A. Pilch Holly B. Meadows Benjamin A. Mardis Prince Mohan Maria Posadas‐Salas Titte Srinivas David J. Taber 《Pharmacotherapy》2017,37(2):159-169
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Effectiveness of an Evidence‐Based Induction Therapy Protocol Revision in Adult Kidney Transplant Recipients
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Jillian P. Casale Dave J. Taber Carmelina Staino Kimberly Boyle Kelly Covert Nicole A. Pilch Caitlin Mardis Holly B. Meadows Kenneth D. Chavin John W. McGillicuddy Prabhakar K. Baliga James N. Fleming 《Pharmacotherapy》2017,37(6):692-699
20.
《中国药房》2019,(15):2105-2110
目的:研究移植患者全血、血浆与血细胞中他克莫司浓度的相关性,并分析移植类型及年龄对三者间他克莫司浓度相关性的影响,为临床合理用药提供参考。方法:随机选取我院20例移植术后使用他克莫司抗排异治疗并进行血药浓度监测的患者,根据移植类型分为肾移植组和肺移植组(各10例),根据年龄分为20~40岁组、41~60岁组和61~80岁组(分别有4、9、7例)。收集患者血药浓度监测的残血,采用化学发光微粒子免疫分析法(CMIA)检测全血中他克莫司谷浓度,并采用超高效液相色谱-串联质谱(UPLC-MS/MS)法同时检测血浆及血细胞中他克莫司浓度。应用散点图矩阵和Spearman秩相关性分析全血与血浆、全血与血细胞、血浆与血细胞中他克莫司浓度的相关性,以及移植类型、年龄对三者间他克莫司浓度相关性的影响。结果:全血与血浆中他克莫司浓度相关性(r=0.623,P<0.01)略强于全血与血细胞中他克莫司浓度的相关性(r=0.591,P<0.01),血浆与血细胞中他克莫司浓度相关性相对较弱(r=0.497,P<0.05)。移植类型、年龄对全血、血浆、血细胞三者间他克莫司浓度相关性均有影响,肾移植组患者全血、血细胞、血浆三者间他克莫司浓度相关性均较弱(r均<0.5),且弱于肺移植组患者;20~40岁组患者全血、血浆、血细胞三者间他克莫司浓度相关性也均较弱(r均<0.3),且均弱于41~60岁组、61~80岁组患者。结论:移植术后患者全血、血浆与血细胞三者间他克莫司浓度的相关性均不强,尤其是肾移植患者和20~40岁年龄段患者,应加强对其排斥反应和不良反应的监测。 相似文献