Tebas Pablo, Bellos Nicholas, Lucasti Christopher, Richmond Gary, Godofsky Eliot, Patel Indravadan, Chiu Yu-Yuan, Evans Claire, Rowell Lucy, Salgo Miklos
University of Pennsylvania, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
J Acquir Immune Defic Syndr. 2008 Mar 1;47(3):342-5. doi: 10.1097/QAI.0b013e31816237f0.
The aim of this study was to examine the influence of kidney disease and hemodialysis on the pharmacokinetics ofenfuvirtide.
An open-label, multicenter, parallel group study of HIV-1-infected patients with varying degrees of kidney dysfunction.
A 90-mg dose of enfuvirtide was administered by subcutaneous injection to 3 groups of patients: group A, patients with normal kidney function; group B, patients with chronic kidney disease; and group C, patients with end-stage renal disease (ESRD) requiring dialysis. Patients with ESRD requiring dialysis received the 90-mg dose of enfuvirtide on 2 separate occasions; a dialysis day and a nondialysis day. After each dose, a full 48-hour pharmacokinetic profile was collected and pharmacokinetic parameters were estimated using model-independent techniques.
Enfuvirtide area under the curve (AUCinfinity) and maximum observed enfuvirtide plasma concentration (Cmax) for patients with normal kidney function (group A) was 49.6 microg h/mL and 3.79 microg/mL, respectively. Patients with chronic kidney disease (group B) had higher AUCinfinity (80.3 microg h/mL) and Cmax (5.72 microg/mL), which was similar to patients with ESRD (group C) on both nondialysis days (AUCinfinity 71.1 microg h/mL; Cmax 5.34 microg/mL) and dialysis days (AUCinfinity 66.9 microg h/mL; Cmax 6.31 microg/mL). An average of< 13% of enfuvirtide was removed during the dialysis procedure. The incidence of adverse events was comparable for all study groups.
Enfuvirtide exposure observed in patients with ESRD requiring dialysis or chronic kidney disease was slightly higher than in patients with normal kidney function and similar to historical Cmax and AUC values from studies in patients with normal kidney function. Thus, enfuvirtide does not require dosage adjustment in patients with impaired kidney function.
本研究旨在探讨肾病和血液透析对恩夫韦肽药代动力学的影响。
一项针对不同程度肾功能不全的HIV-1感染患者的开放标签、多中心、平行组研究。
对3组患者皮下注射90毫克剂量的恩夫韦肽：A组，肾功能正常的患者；B组，慢性肾病患者；C组，需要透析的终末期肾病（ESRD）患者。需要透析的ESRD患者在两个不同的时间接受90毫克剂量的恩夫韦肽；一个透析日和一个非透析日。每次给药后，收集完整的48小时药代动力学曲线，并使用非模型依赖技术估算药代动力学参数。
肾功能正常患者（A组）的恩夫韦肽曲线下面积（AUCinfinity）和观察到的恩夫韦肽血浆最大浓度（Cmax）分别为49.6微克·小时/毫升和3.79微克/毫升。慢性肾病患者（B组）的AUCinfinity（80.3微克·小时/毫升）和Cmax（5.72微克/毫升）较高，这与ESRD患者（C组）在非透析日（AUCinfinity 71.1微克·小时/毫升；Cmax 5.34微克/毫升）和透析日（AUCinfinity 66.9微克·小时/毫升；Cmax 6.31微克/毫升）相似。透析过程中平均<13%的恩夫韦肽被清除。所有研究组不良事件的发生率相当。
需要透析的ESRD患者或慢性肾病患者中观察到的恩夫韦肽暴露量略高于肾功能正常的患者，且与肾功能正常患者研究中的历史Cmax和AUC值相似。因此，肾功能受损的患者无需调整恩夫韦肽的剂量。
