Determination of GHB levels in breast milk and correlation with blood concentrations

The sodium salt of GHB or sodium oxybate is approved and registered in some countries as a therapeutic substance (Xyrem®) for the treatment of narcolepsyassociated 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 5 hours following a 4.5 g 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 0.57 mg/L; 95% Reference Interval (RI): 0.21 – 1.52 mg/L and 0.36 mg/L; 95% RI: 0.13 – 1.03 mg/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 0.5 hour after medication intake was 80.10 mg/L, reaching the peak 1 hour after the drug administration (108.34 mg/L) and it steadily decreased to reach a level of 1.75 mg/L, 5 hours after the medication intake. The GHB concentration found in breast milk followed the same pattern as for the blood, with the highest concentration being 23.19 mg/L, 1 hour after sodium oxybate administration and the lowest 0.99 mg/L, 5 hours 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 3 hours, ranging from 71 to 80% less. It is interesting to note that only at 4 and 5 hours 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 – 1.03 mg/L. Page 4 of 28 Accepted Manuscript We would recommend, following these preliminary data, that nursing mothers under sodium oxybate treatment should breastfeed at least 5 hours after the last GHB administration. However, further studies are necessary in order to confirm these findings.