Pharmacokinetics of sulfobutylether-β-cyclodextrin (SBECD) in subjects on hemodialysis
Pharmacokinetics of sulfobutylether-β-cyclodextrin (SBECD) in subjects on hemodialysis
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DOI：
10.1093/ndt/gfr472
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发表时间：
2012-03-01
影响因子：
6.1
通讯作者：
Damle, Bharat
中科院分区：
文献类型：
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作者：
Luke, David R.;Wood, Nolan D.;Damle, Bharat
背景。在 7 名接受血液透析的终末期肾病男性受试者和 6 名肾功能正常受试者中评估了磺丁基醚-β-环糊精 (SBECD)（静脉注射 (IV) 伏立康唑中的增溶赋形剂）的处置情况。方法。所有受试者按标准伏立康唑剂量每日两次静脉注射伏立康唑[第一天每 12 小时（第 12 小时）6 mg/kg (96 mg/kg SBECD)，随后第 2-4 天第 12 小时 3 mg/kg (48 mg/kg SBECD)，第 5 天早上单次静脉注射]。在选定的给药前谷时间、输注后的选定时间以及第 3 天（非透析）和第 4 天（使用高通量膜透析）集中对受试者进行采样。通过 NONMEM 进行房室分析。结果。 SBECD 处置的特点是二室模型。肾衰竭时，平均中央室容积 (V-1) 和外周室容积 (V-2) 分别为 9.9 升和 6.5 升。正常受试者中，V-1 和 V-2 分别为 9.6 和 5.2 L； SBECD 清除率 (CL) 为 130 mL/min。肾功能衰竭非透析患者的 CL 为 2.6 毫升/分钟，透析期间为 48 毫升/分钟；透析期间平均半衰期从 79 小时缩短至 5 小时（正常受试者：2.1 小时）。结论。血液透析可以显着降低终末期肾病受试者的 SBECD 水平。
Background. The disposition of sulfobutylether-beta-cyclodextrin (SBECD), the solubilizing excipient in intravenous (IV) voriconazole, was assessed in seven male subjects with end-stage renal disease on hemodialysis and six subjects with normal renal function.Methods. All subjects received twice-daily IV voriconazole at the standard voriconazole dose [6 mg/kg (96 mg/kg SBECD) every 12 h (Q12h) on Day I followed by 3 mg/kg (48 mg/kg SBECD) Q12h on Days 2-4, with a single IV dose on the morning of Day 5]. Subjects were sampled at selected pre-dose trough times, at selected times after infusions and intensively on Day 3 (non-dialysis) and Day 4 (dialysis with high-flux membranes). Compartmental analyses were performed by NONMEM.Results. SBECD disposition was characterized by a two-compartment model. In renal failure, mean central (V-1) and peripheral compartment volumes ( V-2) were 9.9 and 6.5 L, respectively. In normal subjects, V-1 and V-2 were 9.6 and 5.2 L, respectively; SBECD clearance (CL) was 130 mL/min. CL in renal failure off-dialysis was 2.6 and 48 mL/min during dialysis; mean half-life decreased from 79 to 5 h during dialysis (normal subjects: 2.1 h).Conclusion. Hemodialysis can significantly reduce levels of SBECD in subjects with end-stage renal disease.