Table 2.

Alterations of AED clearance and/or concentrations during pregnancy: Summary of class I, II, and III studies^a

AED	Reported increases in clearance	Reported decreases in total concentrations	Reported changes in free AED or metabolites
PHT	19–150%	60–70%	Free PHT clearance increased in TM3 by 25%; free PHT concentration decreased by 16–40% in TM3
CBZ	−11 to +27%	0–12%	No change
PB	60%	55%	Decrease in free PB concentration by 50%
PRM	Inconsistent	Inconsistent	Decrease in derived PB concentrations, with lower PB/PRM ratios
VPA	Increased by TM2 and TM3		No change in clearance of free VPA. Free fraction increased by TM2 and TM3
ESX	Inconsistent	Inconsistent
LTG	65–230%, substantial interindividual variability		89% increase in clearance of free LTG
OXC		MHD and active moiety decreased by 36–61%
LEV	243%	60% by TM3

AED, antiepileptic drug; CBZ, carbamazepine; ESX, ethosuximide; LEV, levetiracetam; LTG, lamotrigine; MHD, monohydroxy derivative of oxcarbazepine; OXC, oxcarbazepine; PB, phenobarbital; PHT, phenytoin; PRM, primidone; TM, trimester; VPA, valproic acid.

References:

PHT (Lander et al., 1980; Chen et al., 1982; Bardy et al., 1987; Dickinson et al., 1989; Yerby et al., 1990; Tomson et al., 1994).

CBZ (Battino et al., 1985; Yerby et al., 1985, 1992; Tomson et al., 1994).

PB (Lander et al., 1981; Battino et al., 1984; Yerby et al., 1990; Vajda et al., 2006).

PRM (Rating et al., 1982; Battino et al., 1984).

VPA (Koerner et al., 1989).

ESX (Kuhnz et al., 1984; Tomson et al., 1990).

LTG (Ohman et al., 2000; Tran et al., 2002; de Haan et al., 2004; Pennell et al., 2004, 2007b; Petrenaite et al., 2005).

OXC (Christensen et al., 2006; Mazzucchelli et al., 2006).

LEV (Tomson et al., 2007).

^aFrom Pennell et al., 2007a.