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Lamotrigine clearance increases by 5 weeks gestational age: Relationship to estradiol concentrations and gestational age
Author(s) -
Karanam Ashwin,
Pennell Page B.,
French Jacqueline A.,
Harden Cynthia L.,
Allien Stephanie,
Lau Connie,
Barnard Sarah,
Callisto Samuel P.,
Birnbaum Angela K.
Publication year - 2018
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25321
Subject(s) - medicine , gestational age , gestation , lamotrigine , pregnancy , population , epilepsy , akaike information criterion , obstetrics , biology , statistics , genetics , mathematics , environmental health , psychiatry
Objective To determine how early lamotrigine clearance (LTG‐CL/F) increases during early pregnancy in women with epilepsy and to quantify the relationship of LTG‐CL/F to estradiol concentrations and gestational week. Methods This was a multicenter, observational study of pregnant women with epilepsy on lamotrigine and no interacting concomitant medications, employing frequent blood sampling prior to and early in pregnancy. A population mixed‐effects modeling approach was used to describe the relationship between LTG‐CL/F and gestational week and between LTG‐CL/F and estradiol. Akaike information criterion (AIC) compared goodness of fit between final models and a generalized estimating equation to compare differences between low and high percentage LTG‐CL/F change groups ( p < 0.05). Results Twenty‐five pregnancies (22 participants) were available. Increases in LTG‐CL/F were present at 5 weeks gestational age. Both estradiol and gestational week were highly correlated with LTG‐CL/F changes; LTG‐CL/F increased at the rate of 0.115l/h for every gestational week and 0.844l/h for every 1ng/ml of estradiol, with women in the high LTG‐CL/F percentage change group changing at a faster rate ( p < 0.001). Models using gestational week performed better than models using estradiol. Interpretation Gestational week was a better predictor of changes in LTG‐CL/F than estradiol concentration and may reflect additional factors, although neither was robust enough to use clinically due to substantial interpatient variability. Changes in LTG‐CL/F begin as early as the 5th gestational week, often before women know they are pregnant, emphasizing the importance of planning and early detection of pregnancy and consideration of early implementation of therapeutic drug monitoring. Ann Neurol 2018;84:556–563