Rathbun Chris R, Liedtke Michelle D, Blevins Steve M, Harrison Donald, Lockhart Staci M, Salvaggio Michelle, Acosta Edward P
Department of Clinical and Administrative Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73117, USA.
HIV Clin Trials. 2009 Sep-Oct;10(5):328-36. doi: 10.1310/hct1005-328.
Concurrent atazanavir (ATV) and lopinavir/ritonavir (LPV/r) may be useful for patients with extensive antiretroviral resistance; however, limited information exists concerning the pharmacokinetics and safety of this combination.
A parallel-arm pharmacokinetic study was conducted in HIV-infected patients (n = 10) using contemporary formulations of each agent. Intensive pharmacokinetics were conducted at Day 6 (ATV/r), Day 16 (ATV qd + LPV/r bid), and Day 20 (ATV + LPV/r qd) in Arm A and Day 6 (LPV/r) and Day 12 (LPV/r bid + ATV qd) in Arm B. Plasma ATV, LPV, and ritonavir concentrations were measured by HPLC-UV. Electrocardiograms (12-lead) and safety labs were conducted at each visit.
Prolonged PR and QRS intervals occurred in the majority of patients (mean increase: 16 ms and 5 ms, respectively; p < or = .01). Two patients developed new-onset arrhythmias (bundle branch block, atrioventricular block), resulting in premature termination of the study. No change in ATV or LPV pharmacokinetics was evident.
Concurrent ATV and LPV/r was associated with PR and QRS interval changes in this small study population. Electrocardiogram monitoring should be considered for patients receiving concurrent ATV and LPV/r shortly after their initiation, especially if other risk factors for altered conduction are present.
对于具有广泛抗逆转录病毒耐药性的患者，同时使用阿扎那韦（ATV）和洛匹那韦/利托那韦（LPV/r）可能有效；然而，关于这种联合用药的药代动力学和安全性的信息有限。
在HIV感染患者（n = 10）中进行了一项平行组药代动力学研究，使用每种药物的当代制剂。A组在第6天（ATV/r）、第16天（ATV每日一次 + LPV/r每日两次）和第20天（ATV + LPV/r每日一次）进行强化药代动力学研究，B组在第6天（LPV/r）和第12天（LPV/r每日两次 + ATV每日一次）进行。通过高效液相色谱 - 紫外法测量血浆中ATV、LPV和利托那韦的浓度。每次就诊时进行心电图（12导联）和安全性实验室检查。
大多数患者出现PR和QRS间期延长（平均增加：分别为16毫秒和5毫秒；p≤0.01）。两名患者出现新发心律失常（束支传导阻滞、房室传导阻滞），导致研究提前终止。ATV或LPV的药代动力学没有明显变化。
在这个小研究人群中，同时使用ATV和LPV/r与PR和QRS间期变化有关。对于开始同时使用ATV和LPV/r的患者，尤其是存在其他传导改变危险因素的患者，应考虑进行心电图监测。
