Is infant exposure to antiretroviral drugs during breastfeeding quantitatively important? A systematic review and meta-analysis of pharmacokinetic studies
Is infant exposure to antiretroviral drugs during breastfeeding quantitatively important? A systematic review and meta-analysis of pharmacokinetic studies
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DOI：
10.1093/jac/dkv080
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发表时间：
2015-07-01
影响因子：
5.2
通讯作者：
Else, Laura Jayne
中科院分区：
文献类型：
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作者：
Waitt, Catriona John;Garner, Paul;Else, Laura Jayne
目的：本研究的目的是总结抗逆转录病毒药物的浓度在母乳（BM）和母乳喂养的infants.Methods：这是一个系统的回顾艾滋病毒阳性的妇女服用抗逆转录病毒药物，测量药物在BM的药代动力学研究。使用预定义的标准评估药代动力学和实验室方法的质量。使用广义逆方差法计算合并比值和95% CI，并通过I-2统计量估计异质性。检索了PubMed Central、SCOPUS和LactMed数据库。没有日期或语言限制。截至2014年11月10日进行了审查。通过比较每种药物的推荐治疗剂量与摄入剂量来估计临床相关性。所用的临床和实验室方法以及报告的结果存在显著差异。相对于母体血浆（MP），NRTI在BM中蓄积，BM：MP比值（95% CI估计值）为0.89 - 1.21（14项研究，1159份配对BM和MP样本）。NNRTI估计值为0.71 - 0.94（17项研究，965份配对样本），PI估计值为0.17 - 0.21（8项研究，477份配对样本）。相对于推荐的儿科剂量，母乳喂养的婴儿可能摄入8.4%（95%CI 1.9-15.0），12.5%（95%CI 2.6-22.3）和1.1%（95%CI 0-3.6）的拉米夫定，奈韦拉平和依法韦仑，分别通过BM。结论：转移到未经治疗的婴儿出现定量重要的一些NRTI和NNRTI。药代动力学方法差异很大，我们提出了标准的设计，分析和报告未来的药代动力学研究的药物转移在母乳喂养。
Objectives: The objectives of this study were to summarize antiretroviral drug concentrations in breast milk (BM) and exposure of breast-fed infants.Methods: This was a systematic review of pharmacokinetic studies of HIV-positive women taking antiretrovirals that measured drugs in BM. The quality of pharmacokinetic and laboratory methods was assessed using pre-defined criteria. Pooled ratios and 95% CIs were calculated using the generalized inverse variance method and heterogeneity was estimated by the I-2 statistic. PubMed Central, SCOPUS and LactMed databases were searched. No date or language restrictions were applied. Searches were conducted up to 10 November 2014. Clinical relevance was estimated by comparing ingested dose with the recommended therapeutic dose for each drug.Results: Twenty-four studies were included. There was substantial variability in the clinical and laboratory methods used and in reported results. Relative to maternal plasma (MP), NRTIs accumulate in BM, with BM: MP ratios (95% CI estimates) from 0.89 to 1.21 (14 studies, 1159 paired BM and MP samples). NNRTI estimates were from 0.71 to 0.94 (17 studies, 965 paired samples) and PI estimates were from 0.17 to 0.21 (8 studies, 477 paired samples). Relative to the recommended paediatric doses, a breast-fed infant may ingest 8.4% (95% CI 1.9-15.0), 12.5% (95% CI 2.6-22.3) and 1.1% (95% CI 0-3.6) of lamivudine, nevirapine and efavirenz, respectively, via BM.Conclusions: Transfer to untreated infants appears quantitatively important for some NRTIs and NNRTIs. The pharmacokinetic methods varied widely and we propose standards for the design, analysis and reporting of future pharmacokinetic studies of drug transfer during breastfeeding.