Abstracts

Objective: To determine whether lamotrigine (LTG) clearance is altered during pregnancy. Background: Most established antiepileptic drugs (AEDs) have altered pharmacokinetics during pregnancy. Contributing factors include?absorption,?liver metabolism,?volume of distribution, and ?protein binding. Pregnancy-induced change in liver metabolism has always been thought to affect hydroxylation. LTG is a newer AED which is metabolized primarily by glucoronidation. Whether phamacokinetics of LTG is also affected during pregnancy is unknown. Methods: Charts of 6 women with 7 pregnancies who had been on LTG during pregnancy were reviewed for weight, LTG dose and blood levels at baseline, during pregnancy, and post-partum (pp), and concomitant use of other AEDs and their dosages. Apparent clearance (AC) (L/kg/day) of LTG was calculated by dose/level for time points before pregnancy (baseline), during the 1st, 2nd, and 3rd trimesters (TM), and pp. AC was compared between baseline and 1st TM, 1st and 2nd TM, 2nd and 3rd TM, 1st and 3rd TM, and 3rd TM and pp. Statistical analysis was performed using paired student t-test. Results: Comparison of AC at baseline to the 1st TM was made in 5 pregnancies (1 on monotherapy, 4 on polytherapy with stable doses). There was significant increase (p<0.001) in AC from baseline (mean AC = 0.9955?0.4377) to the 1st TM (1.766?0.4325). All of these patients required dose adjustment during pregnancy for seizure control. There was no significant change in AC between the 1st and 2nd TM, 2nd and 3rd TM, 1st and 3rd TM. Comparison of AC between the 3rd TM and pp was made in 5 pregnancies. This showed a significant decrease in clearance (p<0.001) between the 3rd TM (1.937?1.064) and pp (1.116?0.4794). Conclusion: Pregnancy dramatically increases LTG clearance. This effect occurs early in pregnancy and reverts quickly back to baseline after delivery. Women on LTG must be followed closely during pregnancy and immediately post-partum. Research was supported in part by NIH-NINDS Grant P50 NS16308.