Abstracts

RATIONALE: One of the paramount goals of management of pregnant women with epilepsy is optimal seizure control; 20-37% will experience increased seizures. A major factor is the physiological alterations in antiepileptic drug (AED) metabolism that accompany the pregnant state. Lamotrigine (LTG) is approximately 55% protein bound and is metabolized predominantly by glucuronic acid conjugation. Preliminary reports suggest that LTG clearance may increase early during pregnancy. At the end of this presentation participants should be able to describe the extent and pattern of increased clearance of lamotrigine during pregnancy.
METHODS: Nine patients on LTG monotherapy for epilepsy were studied. All patients had baseline LTG concentration measurements obtained preconception or up to 7 weeks estimated gestational age (EGA), were compliant with medications and blood draws, did not have significant emesis, and were not on any interacting medications. Each patient underwent trough LTG concentration measurements at least monthly. Total LTG concentrations were utilized since LTG is not highly protein-bound. Apparent Clearance (AC) values were calculated as daily dose (mg) / concentration (mg/L). Three patients consistently had weight measurements to allow for calculation of Relative Clearance (daily dose (mg/kg) / concentration (mg/L)).
RESULTS: Forty-four LTG concentration samples were obtained in the 9 women during pregnancy, excluding the baseline samples. AC for each sample was calculated and reported as percentage change from that individual patient[ssquote]s baseline AC (Figure 1). The samples from all 9 women were also grouped together by each trimester and by overall pregnancy and reported as mean percentage change from baseline with standard deviations (Table 1). LTG AC values began to increase very early in pregnancy and steadily and dramatically trended upward to a maximum at term. One patient demonstrated over a 700% increase in AC (Figure 1). Relative (weight-adjusted) Clearance was also calculated for 3 patients and demonstrated the same trend of increased clearance with EGA.
CONCLUSIONS: Our findings of progressively increased LTG clearance throughout pregnancy contradict the previous report of LTG AC increasing in the first trimester only (Epilepsia 2000; 41(suppl 7):246). The extent of increased LTG clearance during pregnancy is far greater than that described with the older AEDs and probably reflects its relatively unique metabolic pathway. Given these findings that alterations in LTG clearance occur substantially yet unpredictably during pregnancy, monthly LTG level monitoring during pregnancy and the postpartum period may be warranted.[table1][figure1]
(Disclosure: Consulting - Dr. Pennell has received consulting fees from GlaxoSmithKline., Honoraria - Dr. Pennell has received honoraria from GlaxoSmithKline.)