抗丙型肝炎病毒阳性患者中环孢素的药代动力学
Cyclosporine pharmacokinetics in anti-HCV+ patients.
作者信息
Wolffenbüttel Luciano, Poli Débora D, Manfro Roberto C, Gonçalves Luiz Felipe S
机构信息
Post-graduation Nephrology Program, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
出版信息
Clin Transplant. 2004 Dec;18(6):654-60. doi: 10.1111/j.1399-0012.2004.00256.x.
BACKGROUND
Cyclosporine (CsA) is a widely used immunosuppressive agent in kidney transplant patients. In Brazil, around 30% of patients awaiting kidney transplantation carry anti-HCV antibodies. Previous observations suggest altered CsA pharmacokinetics in these patients.
METHODS
We conducted two pharmacokinetic studies. In the pre-transplant (pre-Tx) study, we examined 22 dialysis patients on chronic hemodialysis awaiting transplantation, 11 anti-HCV+ [seven polymerase chain reaction (PCR)-positive] matched against 11 controls. In the post-transplant (post-Tx) study, we enrolled 24 kidney allograft recipients - 10 anti-HCV+ (six PCR-positive), and 14 controls. In the first study, all patients received an 8-mg/kg dose of CsA microemulsion (ME). Secondly, the dosage was indicated by the patient's medical team. Pharmacokinetic parameters were calculated from 13 blood samples (0-12 h postdose) by fluorescence polarization immunoassay with specific monoclonal antibodies.
RESULTS
In both studies, maximum concentration (C(max)), minimum concentration (C(min)) and area under the CsA time-concentration curve from 0 to 12 h (AUC(0-12)) were higher for anti-HCV+ patients than for controls, but significantly so only for AUC(0-12) in the pre-Tx study (42%; p < 0.05). When PCR-positive patients were compared with controls, differences were amplified. In the pre-Tx study, differences were 58%, 69%, and 91% higher in PCR-positive patients for C(max) (p = 0.05), AUC(0-12) (p < 0.01), and C(min) (p < 0.01), respectively. In the post-Tx study, results were 50% (p < 0.01) and 32% (p < 0.01) higher in PCR-positive patients for C(max) and AUC(0-12), respectively. In the pre-Tx study, the impact of viremia was significantly higher in female patients. CsA trough levels remained higher along the first year post-transplantation in viremic patients.
CONCLUSIONS
Anti-HCV+ patients, especially those with viremia, present altered CsA pharmacokinetics, with higher peak levels and drug exposure than controls.
背景
环孢素（CsA）是肾移植患者中广泛使用的免疫抑制剂。在巴西，约30%等待肾移植的患者携带抗丙型肝炎病毒（HCV）抗体。先前的观察表明这些患者的CsA药代动力学发生了改变。
方法
我们进行了两项药代动力学研究。在移植前（pre-Tx）研究中，我们检查了22名等待移植的慢性血液透析患者，11名抗HCV阳性患者（7名聚合酶链反应（PCR）阳性）与11名对照匹配。在移植后（post-Tx）研究中，我们纳入了24名肾移植受者——10名抗HCV阳性患者（6名PCR阳性）和14名对照。在第一项研究中，所有患者接受8mg/kg剂量的CsA微乳剂（ME）。其次，剂量由患者的医疗团队确定。通过使用特异性单克隆抗体的荧光偏振免疫分析法，从13份血样（给药后0至12小时）计算药代动力学参数。
结果
在两项研究中，抗HCV阳性患者的最大浓度（C(max)）、最小浓度（C(min)）和0至12小时CsA时间-浓度曲线下面积（AUC(0-12)）均高于对照组，但仅在移植前研究中AUC(0-12)显著升高（42%；p<0.05）。当将PCR阳性患者与对照组进行比较时，差异扩大。在移植前研究中，PCR阳性患者的C(max)（p = 0.05）、AUC(0-12)（p<0.01）和C(min)（p<0.01）分别比对照组高58%、69%和91%。在移植后研究中，PCR阳性患者的C(max)和AUC(0-12)分别比对照组高50%（p<0.01）和32%（p<0.01）。在移植前研究中，病毒血症对女性患者的影响显著更高。病毒血症患者在移植后第一年的CsA谷浓度一直较高。
结论
抗HCV阳性患者，尤其是那些有病毒血症的患者，呈现出改变的CsA药代动力学，其峰值水平和药物暴露高于对照组。
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