STABLE RENAL TRANSPLANT PATIENTS CONVERTED FROM SANDIMMUNE TO NEORAL

稳定的肾移植患者从 SANDIMUNE 转为 NEORAL

• 批准号: 5215686
• 负责人: JOHN C CURTIS
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5215686
• 关键词: clinical research; cyclosporines; dosage; human subject; human therapy evaluation; kidney pharmacology; kidney transplantation

We converted 200 stable renal transplant patients (TXP) from Sandimmune (SAND) to Neoral (NEO) and adjusted dose to maintain a similar trough blood cyclosporine level. Mean age of the TXP was 45.6 +/- 11 years, most (60%) were men, 30% were African-Americans (AAs). Daily (QD) SAND was used in 68% TXPs who converted to BID NEO. A subgroup of 43 TXP on BID SAND was selected because they agreed to blood drawing for 3-hr area-under-the-curve (AUC) studies, before and two months after conversion to NEO. The subgroup had 39% AAs. The entire group showed a 21% (p<0.001) dose reduction by one month with an (p<0.01) increase in trough level -- but marked variability (range = 25% increase to 67% decrease in dose). Logistic regression analysis evaluated factors associated with dose reduction: race, sex, age, BID vs QD regimen and total dose. Two factors were statistically significant predictors: Patients with SAND dose 3 4mg/kg, were 4.9 times more likely to require dose reduction and patients on QD were 2.4 times more likely. Mean reduction in dose was 25% for the QD TXP and 13% for the BID TXP. Interestingly, race was not a predictive factor, even though AAs are reported to be poor absorbers of SAND. Comparison of AAs with Whites in the AUC subgroup showed that AAs and Whites entered the study with similar SAND doses (mg/d) and 12 hr-trough levels. AUC measurements suggested that 17 AAs had better absorption of SAND than 26 whites. Both groups improved after conversion to NEO, with earlier peak levels and higher maximal levels. Whites had a slighter, but not statistically significant, higher AUC after conversion. We conclude: 1) conversion of TXP from SAND to NEO requires a dose reduction to achieve similar trough levels, 2) a high (3 4 mg/kg) SAND dose before conversion is most predictive of need for dose reduction; converting from QD SAND to BID NEO is also predictive, and 3) there is no statistical support for the hypothesis that AAs and Whites differ in absorption of SAND or NEO - both improved after conversion.

我们从 Sandimmune 转化了 200 名稳定的肾移植患者 (TXP) (SAND) 至 Neoral (NEO) 并调整剂量以维持相似的谷值 血环孢素水平。 TXP 的平均年龄为 45.6 +/- 11 岁， 大多数 (60%) 是男性，30% 是非裔美国人 (AA)。 每日（QD）沙子 68% 的 TXP 转换为 BID NEO。 43 TXP 的子组 选择 BID SAND 因为他们同意抽血 3 小时 曲线下面积 (AUC) 研究，之前和之后两个月 转换为 NEO。 该亚组有 39% 的 AA。 整个组的剂量在一个月内减少了 21% (p<0.001) 谷值水平增加（p<0.01）——但变化显着（范围 = 剂量增加 25% 至减少 67%）。 逻辑回归分析 评估与剂量减少相关的因素：种族、性别、年龄、BID 与 QD 方案和总剂量。 两个因素具有统计显着性 预测因素：接受 SAND 剂量 3·4mg/kg 的患者的可能性增加 4.9 倍 需要减少剂量且接受 QD 的患者的可能性增加了 2.4 倍。 QD TXP 的平均剂量减少了 25%，BID TXP 的剂量平均减少了 13%。 有趣的是，种族并不是一个预测因素，尽管 AA 是一个预测因素。 据报道对沙子的吸收能力较差。 AA与白人的比较 AUC 亚组显示，AA 和白人进入研究时 类似的 SAND 剂量（毫克/天）和 12 小时谷值水平。 AUC 测量 表明 17 种 AA 比 26 种白色对沙子有更好的吸收作用。 两个都 转换为 NEO 后各组有所改善，峰值水平较早，并且 更高的最大水平。 白人有轻微的，但没有统计数据 转换后 AUC 显着升高。 我们得出的结论是：1) TXP 从 SAND 转化为 NEO 需要一定剂量 减少以达到类似的谷值水平，2) 高 (3·4 mg/kg) SAND 转换前的剂量最能预测是否需要减少剂量； 从 QD SAND 转换为 BID NEO 也是可预测的，并且 3） 没有统计数据支持 AA 和白人在以下方面存在差异的假设： SAND 或 NEO 的吸收 - 转换后均得到改善。