Magnitude of Lamotrigine Exposure Through Breastfeeding
2Pharmacy Department, Shamir (Assaf Harofeh) Medical Center, ישראל
3Biochemistry Laboratory, Shamir (Assaf Harofeh) Medical Center, ישראל
4Neonatal Intensive Care Unit, Shamir (Assaf Harofeh) Medical Center, ישראל
5Institute of Clinical Pharmacology and Toxicology, Sheba Medical Center
6Department of Medicine A, Sheba Medical Center, ישראל
7Sackler School of Medicine, Tel Aviv University, ישראל
8Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, ישראל
Importance: Lamotrigine use during breastfeeding has significantly increased in the recent years, whereas breastmilk lamotrigine pharmacokinetics data are still sparse.
Objectives: To assess lamotrigine exposure in breastfed infants by monitoring maternal serum and breastmilk concentrations.
Methods: breastfeeding women treated with lamotrigine were recruited to this study. Maternal trough breastmilk and serum samples were collected, and additional breastmilk samples were collected 1,3,6,9,12 hours after lamotrigine consumption. Trough breastmilk/serum ratios (M/S ratio) and breastmilk area under the curve (AUC) values were calculated.
Results: Twenty-one breastfeeding women were recruited to this study, and the final dataset was based on the samples collected from 17 women. Lamotrigine trough serum and mother`s milk concentrations were 5.1±3.3 mg/L and 3.1±1.9 mg/L, respectively (mean±SD). The trough M/S ratio of lamotrigine was 0.66±0.22. The lamotrigine breastmilk average AUC was 41.7±24.6 mg.h/L. The estimated infant dose of lamotrigine was 0.52±0.31 mg/kg/day and 0.26±0.15 mg/kg/day for fully and partially breastfed infants, respectively.
Significant correlation was found between the maternal lamotrigine serum trough concentrations and the breastmilk parameters: trough breastmilk concentrations (Spearman`s rho=0.986, p<0.0001) and breastmilk AUC values (Spearman`s rho=0.941, p<0.0001). No significant correlation was found between the maternal lamotrigine daily dose and serum trough concentrations, breastmilk trough concentrations, and breastmilk AUC values.
Conclusion and relevance: High correlation between the maternal lamotrigine trough serum concentrations and the breastmilk AUC values was found, implying that monitoring the maternal lamotrigine serum concentrations can be useful for prediction of exposure of infants to lamotrigine via the breastmilk.