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OXIDATION – TOXIC PATHWAY (CYP2E1 enzyme) • Only 5-10% of acetaminophen in healthy non-pregnant adults • INCREASES by 80% during pregnancy[⁶⁰] • Creates NAPQI (N-acetyl-p-benzoquinone imine)—the toxic metabolite • NAPQI formation 43% HIGHER in first trimester[⁶⁰] • 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[⁶⁰⁻¹⁰⁰⁻¹⁰¹] Human pharmacokinetic studies reveal dramatic shifts in how pregnant women metabolize acetaminophen: Oxidation to NAPQI (Toxic Pathway) INCREASES by 80% The Brookhuis et al
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