Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, Purpan Hospital University, Toulouse, France (A.A.O., M.-C.C., P.G.); Institut National de la Sante et de la Recherche Medicale, Unité Mixte de Recherche 1037, Pharmacology and Pharmacogenetics Laboratory, University Institute of Cancer Oncopôle, Toulouse, France (A.A.O., E.C.); HIV/Tuberculosis Research and Training Center, University of Science, Techniques and Technologies, Bamako, Mali (A.A.O., A.B., M.M., S.D.); Center for Global Health, Northwestern University, Chicago, Illinois (M.M., R.L.M.); Department of Pediatric, University Hospital of Gabriel Touré, Bamako, Mali (K.B.-M., M.S.); Referral Health Center V, Bamako, Mali (Z.D.); and Institut National de la Recherche Agronomique Unité Mixte de Recherche 1331-TOXALIM, Veterinary School of Toulouse, Toulouse, France (P.G.)
Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, Purpan Hospital University, Toulouse, France (A.A.O., M.-C.C., P.G.); Institut National de la Sante et de la Recherche Medicale, Unité Mixte de Recherche 1037, Pharmacology and Pharmacogenetics Laboratory, University Institute of Cancer Oncopôle, Toulouse, France (A.A.O., E.C.); HIV/Tuberculosis Research and Training Center, University of Science, Techniques and Technologies, Bamako, Mali (A.A.O., A.B., M.M., S.D.); Center for Global Health, Northwestern University, Chicago, Illinois (M.M., R.L.M.); Department of Pediatric, University Hospital of Gabriel Touré, Bamako, Mali (K.B.-M., M.S.); Referral Health Center V, Bamako, Mali (Z.D.); and Institut National de la Recherche Agronomique Unité Mixte de Recherche 1331-TOXALIM, Veterinary School of Toulouse, Toulouse, France (P.G.).
J Pharmacol Exp Ther. 2018 Sep;366(3):479-484. doi: 10.1124/jpet.118.249938. Epub 2018 Jul 9.
Limited data are currently available on antiretroviral pharmacokinetics in breast milk (BM) and in breastfed infants' blood. To explore these parameters in patients in Mali, we measured plasma antiretroviral levels in human immunodeficiency virus (HIV)-infected mothers and their breastfed infants over 6 months. We specifically analyzed the concentrations of efavirenz (EFV) and lopinavir (LPV) in the plasma of mothers living with HIV and their breastfed infants. Blood samples were collected at delivery and at month 1, 3, and 6 postpartum. EFV and LPV concentrations were measured by liquid chromatography-tandem mass spectrometry. HIV-1 RNA load was measured by Abbott M2000RT RealTime System at delivery and 6 months postpartum for mothers, and at 3 and 6 months postbirth for infants. The median duration of antiretroviral therapy at study inclusion was 57 months [interquartile range (IQR), 0-168 months]. The median EFV ratios of infant plasma/maternal plasma (MP) were 0.057 at month 1, 0.072 at month 3, and 0.048 at month 6. During the study period, the median BM/MP ratio of EFV was 1.16 (IQR, 0.96-20.62), which corresponds to a relative infant dose of 2.46% of the recommended weight-adjusted pediatric EFV dose at month 6. The apparent infant clearance of EFV was 0.146 l/h per kilogram at month 6. The LPV concentrations in the plasma of all infants were undetectable. No drug-related adverse reaction or toxicity was observed in any of the infants. The two women who presented a viral load of >50 copies/ml at month 6 had undetectable plasma drug concentrations at the same period. This study showed that breastfed infants received a low level of EFV but not LPV from their treated mothers.
目前有关人乳（BM）和母乳喂养婴儿血液中抗逆转录病毒药代动力学的数据有限。为了在马里的患者中探索这些参数，我们在 6 个月内测量了感染人类免疫缺陷病毒（HIV）的母亲及其母乳喂养婴儿的血浆抗逆转录病毒水平。我们专门分析了接受抗逆转录病毒治疗的 HIV 感染母亲及其母乳喂养婴儿的血浆中依非韦伦（EFV）和洛匹那韦（LPV）的浓度。在分娩时以及产后第 1、3 和 6 个月采集血样。通过液相色谱-串联质谱法测量 EFV 和 LPV 的浓度。在分娩时和产后 6 个月为母亲，以及在产后 3 和 6 个月为婴儿，使用 Abbott M2000RT RealTime 系统测量 HIV-1 RNA 载量。在研究纳入时，抗逆转录病毒治疗的中位持续时间为 57 个月[四分位距（IQR），0-168 个月]。婴儿血浆/母亲血浆（MP）中 EFV 的中位数比值在第 1 个月时为 0.057，第 3 个月时为 0.072，第 6 个月时为 0.048。在研究期间，EFV 的中位 BM/MP 比值为 1.16（IQR，0.96-20.62），这相当于第 6 个月时体重调整后推荐儿童 EFV 剂量的相对婴儿剂量为 2.46%。婴儿 EFV 的表观清除率在第 6 个月时为 0.146 l/h/kg。所有婴儿的 LPV 血浆浓度均无法检测到。在任何婴儿中均未观察到与药物相关的不良反应或毒性。在第 6 个月时病毒载量＞50 拷贝/ml 的两名妇女在同一时期血浆药物浓度无法检测到。这项研究表明，接受治疗的母亲母乳喂养的婴儿从母亲那里获得的 EFV 水平较低，但不能获得 LPV。
