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OXIDATION TOXIC PATHWAY (CYP2E1 enzyme) Only 5-10% of acetaminophen in healthy non-pregnant adults INCREASES by 80% during pregnancy[] Creates NAPQI (N-acetyl-p-benzoquinone imine)the toxic metabolite NAPQI formation 43% HIGHER in first trimester[] NAPQI must be immediately neutralized by glutathione When glutathione is depleted, NAPQI causes cellular damage Crosses the placenta and damages fetal brain HOW PREGNANCY CHANGES ACETAMINOPHEN METABOLISM METABOLIC PATHWAY CHANGES DURING PREGNANCY[] Human pharmacokinetic studies reveal dramatic shifts in how pregnant women metabolize acetaminophen: Oxidation to NAPQI (Toxic Pathway) INCREASES by 80% The Brookhuis et al