Abstracts

Several retrospective studies have reported significant increases in apparent clearance (Cl) of lamotrigine (LTG) during pregnancy. Such an increase has been shown to be progressive until the 32nd week of gestation, followed by a rapid return postpartum to preconception levels. Failure to adjust LTG doses to the increase in Cl yields lower serum concentrations and may result in seizures. The aim of our study was to evaluate the LTG dose adjustments required across trimesters (TMs) to maintain preconception levels in a cohort remaining seizure free during pregnancy., A retrospective chart review study resulted in four patients meeting the following criteria: stable dose of LTG and seizure free state for at least one month prior to conception, LTG monotherapy or one adjunct AED with no known pharmacokinetic interactions. Adjunct AED dose was not adjusted during pregnancy. No concomitant drug therapy interfering with metabolic pathway of LTG. At least one documented LTG serum level at steady state (Css) and wt. per TM. No known seizures during pregnancy. LTG dose adjustments were only made in an attempt to maintain preconception levels. For each TM the following mean values were recorded for each pt.: wt., dose (in mg/kg), and LTG Css. LTG Cl was calculated with the equation: CL=dose (mg/kg/day)/LTG Css. Data were analyzed using a Friedman[apos]s ANOVA with post-hoc comparisons using a Wilcoxon Signed Ranks Test. LTG values were normalized for weight (LTG/wt). This value was our primary outcome variable. We also compared serum LTG levels across TMs to assess if preconception values were maintained., Serum LTG levels (median per TM: 1st =5.6, range 5.8; 2nd=7.6, range 5.8; 3rd=7.6, range 12.6) did not change significantly across TMs (X[sup2]=1.50, p=.47). LTG dose/wt (median per TM: 1st=8.6mg/kg, range 5.9mg/kg; 2nd=12.5mg/kg, range 14.3mg/kg; 3rd=14.3mg/kg, range 12.9mg/kg) was significantly different across TMs (X[sup2]=8.0, p=.02). Post-hoc comparisons revealed significant increase in LTG dose/wt from 1st to 2nd TM (Z= -1.83, p=.03 one-tailed) and between 2nd and 3rd TM (Z=-1.83, p=.03 one-tailed). Median increase in dose/wt from 1st to 2nd TM was 3.91mg/kg/day (range= 8.4), and median increase from 2nd to 3rd TM was 1.96mg/kg/day (range=1.61)., Increments of LTG dose across TMs can maintain preconception LTG levels throughout pregnancy. The required increase appeared greater between the 1st and 2nd TM than between the 2nd and 3rd TM, although our limited sample size precludes formal statistical analysis of these differences. This may appear counterintuitive as increased blood volume in the 3rd TM would seem to necessitate a larger increase in LTG dose. However, we controlled for this by normalizing LTG dose for wt. (LTG/wt). These results suggest that significant increases in LTG dose/wt are required to maintain preconception LTG serum levels across TM. Presently prospective data is being collected to expand on these findings.,