Lamotrigine clearance during pregnancy.
OBJECTIVE
To evaluate changes in lamotrigine (LTG) clearance before, during, and after pregnancy.


METHODS
Twelve pregnancies that had complete steady-state data before, during, and after pregnancy were evaluated. Data included weight, LTG dose, and LTG blood levels at preconception, during pregnancy, and postpartum, and concomitant use of other antiepileptic drugs and their dosages. Apparent clearance (L/[kg.day]) of LTG was calculated by dose/level/weight for time points at preconception; during the first trimester, second trimester, and third trimester; and postpartum. Apparent clearance was compared between preconception and each of the three trimesters. Statistical analysis was performed using one-way analysis of variance, the Student-Newman-Keuls test, and the paired Student's t-test.


RESULTS
An increase in apparent clearance (>65%) was observed between preconception and the second and third trimesters (p < 0.05). Eleven pregnancies required higher doses of LTG to maintain therapeutic levels during pregnancy. There was no significant change in apparent clearance between each trimester. A decrease in apparent clearance was observed between the last two trimesters and postpartum (p < 0.05). In the postpartum period, apparent clearances returned to the preconception baseline, and LTG doses needed to be reduced.


CONCLUSIONS
Pregnancy increases LTG clearance by >50%. This effect occurs early in pregnancy and reverts quickly after delivery. LTG levels should be monitored before, during, and after pregnancy.
Tran
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MINCEP Epilepsy Care, University of Minnesota, Minneapolis, MN 55416, USA.
Leppik
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Blesi
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Sathanandan
S T
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Remmel
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D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood* / Q000188:drug therapy; D011446:Prospective Studies; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine