Pescovitz M D, First M R
Department of Surgery, Indiana University, Indianapolis, IN 46202-5250, USA.
Transpl Int. 1998;11 Suppl 1:S94-7. doi: 10.1007/s001470050435.
Variability in cyclosporine drug exposure of > or = 20% has been shown to be a risk factor for the development of chronic renal allograft rejection. We tested the hypothesis that a cyclosporine microemulsion (CsA-ME) would result in reduced variability in stable maintenance renal transplant patients when compared with the original formulation of cyclosporine (CsA).
The 31 maintenance renal transplant recipients were part of a multicenter, randomized, double-blind, prospective study comparing the CsA formulation with the CsA-ME formulation. Pharmacokinetics analyses were performed at two centers 1, 4, 12, and 52 weeks after patients were randomized to continue receiving CsA or to convert to CsA-ME.
The means of the week 1-, 4-, and 12-week areas under the concentration-time curves (AUC), and Cmax were significantly higher and the Tmax was significantly shorter in those patients converted to CsA-ME than in those remaining on CsA. There was no correlation between change in AUC after conversion and change in serum creatinine. The coefficient of variation values for dose-adjusted AUC, expressed as a percentage (%CVAUC), were lower in CsA-ME patients than CsA patients after both 12 and 52 weeks. Over the initial 12 weeks. %CVAUC values of < or = 20% were seen in a significantly greater proportion of CsA-ME patients than CsA patients.
Conversion of maintenance renal transplant recipients from CsA to CsA-ME resulted in improved absorption of cyclosporine. The CsA-ME formulation resulted in long-term reduction in the variability of cyclosporine exposure and more consistent pharmacokinetics.
环孢素药物暴露变异性≥20%已被证明是慢性肾移植排斥反应发生的一个危险因素。我们检验了这样一个假设，即与环孢素原制剂（CsA）相比，环孢素微乳剂（CsA-ME）可降低稳定期维持性肾移植患者的变异性。
31名维持性肾移植受者参与了一项多中心、随机、双盲、前瞻性研究，该研究比较了CsA制剂与CsA-ME制剂。在患者被随机分组继续接受CsA或转换为CsA-ME后的1、4、12和52周，在两个中心进行了药代动力学分析。
转换为CsA-ME的患者在第1、4和12周的浓度-时间曲线下面积（AUC）均值和Cmax显著更高，Tmax显著更短，而继续使用CsA的患者则不然。转换后AUC的变化与血清肌酐的变化之间无相关性。在12周和52周后，CsA-ME患者剂量调整后的AUC变异系数值（以百分比表示，%CVAUC）低于CsA患者。在最初的12周内，CsA-ME患者中%CVAUC值≤20%的比例显著高于CsA患者。
维持性肾移植受者从CsA转换为CsA-ME可改善环孢素的吸收。CsA-ME制剂可长期降低环孢素暴露的变异性，并使药代动力学更一致。
