Murtagh Ross, Else Laura J, Kuan Kenneth Bk, Khoo Saye H, Jackson Valerie, Patel Anjali, Lawler Marguerite, McDonald Grainne, Le Blanc David, Avramovic Gordana, Redmond Niamh, Lambert John S
School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Antivir Ther. 2019;24(3):229-233. doi: 10.3851/IMP3291.
Physiological changes during pregnancy can have a significant impact on antiretroviral pharmacokinetics (PK), which may result in reduced drug efficacy. Here we describe the PK of darunavir/ritonavir (DRV/r) 800/100 once daily in a cohort of pregnant women undergoing routine therapeutic drug monitoring (TDM) as well as transplacental passage of DRV by measuring and comparing cord blood and maternal blood samples at delivery.
Pregnant HIV-positive women received DRV/r as part of routine pre-natal care. Demographic and clinical data were collected. DRV plasma concentrations [DRV] were determined in the first (T1), second (T2) and third (T3) trimester and at postpartum (PP). The target concentration was 550 ng/ml. Where possible, paired maternal and cord blood samples were taken at delivery.
A total of 33 women were enrolled. Samples were taken 14-20 h post-dose and measured concentrations were extrapolated to 24 h post-dose. At the time nearest to delivery, all but four had undetectable plasma viral loads (pVL). [DRV] were determined in 1 (T1); 14 (T2); 32 (T3) and 29 (PP). 1 sample was <550 ng/ml at T2, 6 at T3 and 3 at PP. [DRV] were significantly lower at T2/T3 relative to PP.
[DRV] in T2 and T3 were 36-55% when compared with PP. However, DRV PK in pregnancy were not associated with a lack of virological suppression at delivery as of the 33 patients enrolled in this study, 31 had no HIV transmission from mother to child. Data regarding two candidates were not available as they delivered in a separate health-care facility.
孕期的生理变化会对抗逆转录病毒药物的药代动力学（PK）产生重大影响，这可能导致药物疗效降低。在此，我们描述了在一组接受常规治疗药物监测（TDM）的孕妇中，每日一次服用800/100达芦那韦/利托那韦（DRV/r）的药代动力学情况，以及通过在分娩时测量和比较脐带血与母体血样来研究DRV的胎盘转运情况。
HIV阳性孕妇在常规产前护理中接受DRV/r治疗。收集人口统计学和临床数据。在孕早期（T1）、孕中期（T2）、孕晚期（T3）及产后（PP）测定DRV血浆浓度[DRV]。目标浓度为550 ng/ml。在可能的情况下，分娩时采集配对的母体和脐带血样本。
共纳入33名女性。在给药后14 - 20小时采集样本，并将测得的浓度外推至给药后24小时。在最接近分娩时，除4人外，所有孕妇的血浆病毒载量（pVL）均不可检测。在T1期测定了1例[DRV]；T2期测定了14例；T3期测定了32例；PP期测定了29例。T2期有1个样本<550 ng/ml，T3期有6个，PP期有3个。与PP期相比，T2/T3期的[DRV]显著降低。
与PP期相比，T2期和T3期的[DRV]为36% - 55%。然而，本研究纳入的33例患者中，孕期DRV的药代动力学与分娩时病毒学抑制缺乏无关，因为31例母婴未发生HIV传播。另外两名患者在另一家医疗机构分娩，未获得相关数据。
