Department of Medicine, University of North Carolina, Chapel Hill, NC 27599-7215, USA.
J Acquir Immune Defic Syndr. 2013 May 1;63(1):51-8. doi: 10.1097/QAI.0b013e31827fd47e.
To investigate the intraindividual pharmacokinetics (PKs) of total (protein bound plus unbound) and unbound lopinavir/ritonavir (LPV/RTV) and to assess whether the pediatric formulation (100 mg/25 mg) can overcome any pregnancy-associated changes.
Prospective longitudinal PK study.
HIV-infected pregnant antiretroviral therapy-naive and experienced women receiving LPV/RTV 400 mg/100 mg tablets twice daily. Intensive PK evaluations were performed at 20-24 weeks (PK1), 30 weeks (PK2) followed by empiric dose increase using the pediatric formulation (100 mg/25 mg twice daily), 32 weeks (PK3), and 8 weeks postpartum (PK4).
Twelve women completed prespecified PK evaluations. Median (range) age was 28 (18-35) years and baseline BMI was 32 (19-41) kg/m. During pregnancy, total area under the time concentration (AUC0-12h) for LPV was significantly lower than postpartum (PK1, PK2, or PK3 vs. PK4, P = 0.005). Protein-unbound LPV AUC0-12h remained unchanged during pregnancy [PK1: 1.6 (1.3-1.9) vs. PK2: 1.6 (1.3-1.9) μg·h/mL, P = 0.4] despite a 25% dose increase [PK2 vs. PK3: 1.8 (1.3-2.1) μg·h/mL, P = 0.5]. Protein-unbound LPV predose concentrations (C12h) did not significantly change despite dose increase [PK2: 0.10 (0.08-0.15) vs. PK3: 0.12 (0.10-0.15) μg/mL, P = 0.09]. Albumin and LPV AUC0-12h fraction unbound were correlated (rs = 0.3, P = 0.03).
Total LPV exposure was significantly decreased throughout pregnancy despite the increased dose. However, the exposure of unbound LPV did not change significantly regardless of trimester or dose. Predose concentrations of unbound LPV were not affected by the additional dose and were 70-fold greater than the minimum efficacy concentration. These findings suggest dose adjustments may not be necessary in all HIV-infected pregnant women.
研究全（结合蛋白加游离）和游离洛匹那韦/利托那韦（LPV/RTV）的个体内药代动力学（PKs），并评估儿科制剂（100mg/25mg）是否能克服任何与妊娠相关的变化。
前瞻性纵向 PK 研究。
HIV 感染的接受抗逆转录病毒治疗的初治和经验丰富的孕妇，每天服用 LPV/RTV 400mg/100mg 片剂两次。在 20-24 周（PK1）、30 周（PK2）时进行强化 PK 评估，然后根据经验使用儿科制剂（100mg/25mg，每日两次）增加剂量，在 32 周（PK3）和产后 8 周（PK4）进行评估。
12 名女性完成了规定的 PK 评估。中位（范围）年龄为 28 岁（18-35 岁），基线 BMI 为 32kg/m。在妊娠期间，LPV 的总 AUC0-12h 明显低于产后（PK1、PK2 或 PK3 与 PK4，P=0.005）。尽管剂量增加了 25%，但妊娠期间游离 LPV 的 AUC0-12h 仍保持不变[PK1：1.6（1.3-1.9）vs. PK2：1.6（1.3-1.9）μg·h/mL，P=0.4]（PK2 与 PK3：1.8（1.3-2.1）μg·h/mL，P=0.5）。尽管剂量增加，游离 LPV 的预剂量浓度（C12h）也没有明显变化[PK2：0.10（0.08-0.15）vs. PK3：0.12（0.10-0.15）μg/mL，P=0.09]。白蛋白和 LPV AUC0-12h 游离分数呈相关（rs=0.3，P=0.03）。
尽管增加了剂量，但 LPV 的总暴露在整个妊娠期间都明显降低。然而，游离 LPV 的暴露水平无论在哪个孕期或剂量下都没有显著变化。游离 LPV 的预剂量浓度不受额外剂量的影响，比最低疗效浓度高 70 倍。这些发现表明，并非所有 HIV 感染的孕妇都需要调整剂量。
