Lamotrigine clearance increases by 5 weeks gestational age: Relationship to estradiol concentrations and gestational age

ObjectiveTo 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.MethodsThis 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 a nd high percentage LTG‐CL/F change groups (p <  0.05).ResultsTwenty ‐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 1n g/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.InterpretationGestational week was a better predictor of changes in LTG ‐CL/F than estradiol concentration and may reflect additional factors, although neither was robust e...
Source: Annals of Neurology - Category: Neurology Authors: Tags: Research Article Source Type: research