Busardò Francesco Paolo, Bertol Elisabetta, Mannocchi Giulio, Tittarelli Roberta, Pantano Flaminia, Vaiano Fabio, Baglio Giovanni, Kyriakou Chrystalla, Marinelli Enrico
Unit of Forensic Toxicology (UoFT) - Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, Italy.
Department of Health Science, Forensic Toxicology Division, University of Florence, Florence, Italy.
Forensic Sci Int. 2016 Aug;265:172-81. doi: 10.1016/j.forsciint.2016.02.020. Epub 2016 Feb 17.
The sodium salt of GHB or sodium oxybate is approved and registered in some countries as a therapeutic substance (Xyrem(®)) for the treatment of narcolepsy-associated cataplexy. This study was designed to measure the GHB endogenous levels in blood and breast milk of 20 breastfeeding women. In addition, blood and breast milk samples of a 32-year-old narcoleptic nursing mother, who was on sodium oxybate treatment, were simultaneously collected at 0.5, 1, 3, 4 and 5h following a 4.5g GHB dose and analyzed, in order to establish the safety interval of time to breastfeed. A GC-MS method for the detection and quantification of GHB in blood and breast milk was developed and fully validated. The geometric mean of endogenous GHB levels in blood and breast milk detected at time 0 were 0.57mg/L; 95% Reference Interval (RI): 0.21-1.52mg/L and 0.36mg/L; 95% RI: 0.13-1.03mg/L, respectively. The geometric mean of the concentration of GHB in milk was 37% less (95% RI: from 14 to 53%) compared to that found in the blood. The analysis of blood and breast milk samples collected from the 32 years-old female showed the following results: GHB blood concentration 0.5h after medication intake was 80.10mg/L, reaching the peak 1h after the drug administration (108.34mg/L) and it steadily decreased to reach a level of 1.75mg/L, 5h after the medication intake. The GHB concentration found in breast milk followed the same pattern as for the blood, with the highest concentration being 23.19mg/L, 1h after sodium oxybate administration and the lowest 0.99mg/L, 5h after the medication's intake. The comparison between blood and breast milk GHB levels in the 32-year-old woman, showed significant lower GHB levels in milk at 0.5, 1 and 3h, ranging from 71 to 80% less. It is interesting to note that only at 4 and 5h the difference between blood and breast milk GHB levels fell within the 95% RI (14-53%) of endogenous levels. Taking into consideration the absence of reference values for endogenous GHB in milk, we suggest the following reference interval: 0.13-1.03mg/L. We would recommend, following these preliminary data, that nursing mothers under sodium oxybate treatment should breastfeed at least 5h after the last GHB administration. However, further studies are necessary in order to confirm these findings.
γ-羟基丁酸（GHB）的钠盐或羟丁酸钠在一些国家被批准并注册为一种治疗物质（Xyrem(®)），用于治疗发作性睡病相关的猝倒症。本研究旨在测量20名哺乳期妇女血液和母乳中的内源性GHB水平。此外，还同时采集了一名32岁正在接受羟丁酸钠治疗的发作性睡病哺乳期母亲在服用4.5克GHB剂量后的0.5、1、3、4和5小时的血液和母乳样本并进行分析，以确定母乳喂养的安全时间间隔。开发并充分验证了一种用于检测和定量血液及母乳中GHB的气相色谱-质谱（GC-MS）方法。在时间0检测到的血液和母乳中内源性GHB水平的几何平均值分别为0.57毫克/升；95%参考区间（RI）：0.21 - 1.52毫克/升和0.36毫克/升；95% RI：0.13 - 1.03毫克/升。母乳中GHB浓度的几何平均值比血液中低37%（95% RI：14%至53%）。对从这位32岁女性采集的血液和母乳样本的分析显示了以下结果：服药后0.5小时GHB血液浓度为80.10毫克/升，给药后1小时达到峰值（108.34毫克/升），服药后5小时稳步下降至1.75毫克/升。母乳中发现的GHB浓度与血液遵循相同模式，羟丁酸钠给药后1小时最高浓度为23.19毫克/升，服药后5小时最低为0.99毫克/升。对这位32岁女性血液和母乳中GHB水平的比较显示，在0.5、1和3小时时母乳中的GHB水平显著较低，降低幅度在71%至80%之间。有趣的是，仅在4和5小时时，血液和母乳中GHB水平的差异落在内源性水平的95% RI（14% - 53%）范围内。考虑到母乳中内源性GHB缺乏参考值，我们建议以下参考区间：0.13 - 1.03毫克/升。根据这些初步数据，我们建议正在接受羟丁酸钠治疗的哺乳期母亲应在最后一次服用GHB后至少5小时再进行母乳喂养。然而，需要进一步研究以证实这些发现。
