Salem Ahmed Hamed, Jones Aksana Kaefer, Santini-Oliveira Marilia, Taylor Graham P, Patterson Kristine B, Nilius Angela M, Klein Cheri Enders
Clinical Pharmacology and Pharmacometrics, AbbVie, North Chicago, Illinois, USA Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
Clinical Pharmacology and Pharmacometrics, AbbVie, North Chicago, Illinois, USA.
Antimicrob Agents Chemother. 2015 Nov 2;60(1):400-8. doi: 10.1128/AAC.01197-15. Print 2016 Jan.
Lopinavir-ritonavir is frequently prescribed to HIV-1-infected women during pregnancy. Decreased lopinavir exposure has been reported during pregnancy, but the clinical significance of this reduction is uncertain. This analysis aimed to evaluate the need for lopinavir dose adjustment during pregnancy. We conducted a population pharmacokinetic analysis of lopinavir and ritonavir concentrations collected from 84 pregnant and 595 nonpregnant treatment-naive and -experienced HIV-1-infected subjects enrolled in six clinical studies. Lopinavir-ritonavir doses in the studies ranged between 400/100 and 600/150 mg twice daily. In addition, linear mixed-effect analysis was used to compare the area under the concentration-time curve from 0 to 12 h (AUC0-12) and concentration prior to dosing (Cpredose) in pregnant women and nonpregnant subjects. The relationship between lopinavir exposure and virologic suppression in pregnant women and nonpregnant subjects was evaluated. Population pharmacokinetic analysis estimated 17% higher lopinavir clearance in pregnant women than in nonpregnant subjects. Lopinavir clearance values postpartum were 26.4% and 37.1% lower than in nonpregnant subjects and pregnant women, respectively. As the tablet formulation was estimated to be 20% more bioavailable than the capsule formulation, no statistically significant differences between lopinavir exposure in pregnant women receiving the tablet formulation and nonpregnant subjects receiving the capsule formulation were identified. In the range of lopinavir AUC0-12 or Cpredose values observed in the third trimester, there was no correlation between lopinavir exposure and viral load or proportion of subjects with virologic suppression. Similar efficacy was observed between pregnant women and nonpregnant subjects receiving lopinavir-ritonavir at 400/100 mg twice daily. The pharmacokinetic and pharmacodynamic results support the use of a lopinavir-ritonavir 400/100-mg twice-daily dose during pregnancy.
洛匹那韦 - 利托那韦常用于孕期感染HIV - 1的女性。有报道称孕期洛匹那韦的药物暴露量降低，但其降低的临床意义尚不确定。本分析旨在评估孕期洛匹那韦剂量调整的必要性。我们对六项临床研究中纳入的84名孕期及595名未接受过治疗和接受过治疗的非孕期HIV - 1感染受试者所采集的洛匹那韦和利托那韦浓度进行了群体药代动力学分析。研究中的洛匹那韦 - 利托那韦剂量为每日两次，每次400/100至600/150毫克。此外，采用线性混合效应分析比较了孕妇和非孕妇0至12小时浓度 - 时间曲线下面积（AUC0 - 12）以及给药前浓度（Cpredose）。评估了孕妇和非孕妇中洛匹那韦暴露与病毒学抑制之间的关系。群体药代动力学分析估计，孕妇的洛匹那韦清除率比非孕妇高17%。产后洛匹那韦清除率值分别比非孕妇和孕妇低26.4%和37.1%。由于估计片剂剂型的生物利用度比胶囊剂型高20%，因此在接受片剂剂型的孕妇和接受胶囊剂型的非孕妇之间，未发现洛匹那韦暴露量存在统计学上的显著差异。在孕晚期观察到的洛匹那韦AUC0 - 12或Cpredose值范围内，洛匹那韦暴露与病毒载量或病毒学抑制受试者比例之间无相关性。每日两次接受400/100毫克洛匹那韦 - 利托那韦的孕妇和非孕妇之间观察到相似的疗效。药代动力学和药效学结果支持孕期使用每日两次400/100毫克的洛匹那韦 - 利托那韦剂量。
