*Department of Pediatrics, Boston University School of Medicine, Boston, MA; †Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD; ‡HIV/AIDS Research Department, Irmandade da Santa Casa de Misericordia de Porto Alegre, Rio Grande do Sul, Brazil; §Department of Pediatrics, David Geffen UCLA School of Medicine, Los Angeles, CA; ‖Malawi College of Medicine, Blantyre, Malawi; ¶Infectious Diseases Department, Hospital Federal dos Servidores do Estado, Rio de Janiero, Brazil; #Department of Pediatrics, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; **Serviço de Infectologia, Hospital Nossa Senhora da Conceicao, Porto Alegre, Rio Grande do Sul, Brazil; ††Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; ‡‡Gilead Sciences, Foster City, CA; §§Statistical Center for HIV/AIDS Research and Prevention, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; ‖‖Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; ¶¶Family Health International, Durham, NC; ##Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda; ***National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; and †††Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD.
J Acquir Immune Defic Syndr. 2014 Jan 1;65(1):33-41. doi: 10.1097/QAI.0b013e3182a921eb.
Data describing the pharmacokinetics and safety of tenofovir in neonates are lacking.
The HIV Prevention Trials Network 057 protocol was a phase 1, open-label study of the pharmacokinetics and safety of tenofovir disoproxil fumarate (TDF) in HIV-infected women during labor and their infants during the first week of life with 4 dosing cohorts: maternal 600 mg doses/no infant dosing; no maternal dosing/infant 4 mg/kg doses on days 0, 3, and 5; maternal 900 mg doses/infant 6 mg/kg doses on days 0, 3, and 5; maternal 600 mg doses/infant 6 mg/kg daily for 7 doses. Pharmacokinetic sampling was performed on cohort 1 and 3 mothers and all infants. Plasma, amniotic fluid, and breast milk tenofovir concentrations were determined by liquid chromatographic-tandem mass spectrometric assay. The pharmacokinetic target was for infant tenofovir concentration throughout the first week of life to exceed 50 ng/mL, the median trough tenofovir concentration in adults receiving standard chronic TDF dosing.
One hundred twenty-two mother-infant pairs from Malawi and Brazil were studied. Tenofovir exposure in mothers receiving 600 and 900 mg exceeded that in nonpregnant adults receiving standard 300 mg doses. Tenofovir elimination in the infants was equivalent to that in older children and adults, and trough tenofovir plasma concentrations exceeded 50 ng/mL in 74%-97% of infants receiving daily dosing.
A TDF dosing regimen of 600 mg during labor and daily infant doses of 6 mg/kg maintains infant tenofovir plasma concentration above 50 ng/mL throughout the first week of life and should be used in the studies of TDF efficacy for HIV prevention of mother-to-child transmission and early infant treatment.
缺乏关于替诺福韦在新生儿中的药代动力学和安全性的数据。
HIV 预防试验网络 057 方案是一项关于替诺福韦二吡呋酯（TDF）在分娩期间感染 HIV 的女性及其婴儿在生命的第一周内药代动力学和安全性的 1 期、开放标签研究，共有 4 个剂量组：母亲 600mg 剂量/无婴儿剂量；无母亲剂量/婴儿在第 0、3 和 5 天 4mg/kg 剂量；母亲 900mg 剂量/婴儿在第 0、3 和 5 天 6mg/kg 剂量；母亲 600mg 剂量/婴儿在第 0、3 和 5 天 6mg/kg 剂量，每天 7 剂。对队列 1 和 3 的母亲和所有婴儿进行了药代动力学采样。通过液相色谱-串联质谱法测定血浆、羊水和母乳中替诺福韦浓度。婴儿在生命的第一周内的药代动力学目标是替诺福韦浓度超过 50ng/ml，这是接受标准慢性 TDF 剂量的成人中替诺福韦的中位谷浓度。
来自马拉维和巴西的 122 对母婴进行了研究。接受 600 和 900mg 剂量的母亲的替诺福韦暴露量超过接受标准 300mg 剂量的非妊娠成人。婴儿替诺福韦的消除与年龄较大的儿童和成人相当，每天接受剂量的婴儿中 74%-97%的婴儿替诺福韦谷血浆浓度超过 50ng/ml。
在分娩期间给予 TDF 600mg 剂量，以及每天给予婴儿 6mg/kg 剂量，可以使婴儿在生命的第一周内维持替诺福韦血浆浓度超过 50ng/ml，并且应该在 TDF 预防母婴传播和早期婴儿治疗的疗效研究中使用。
