Cytochrome P450 (CYP) 2E1–mediated clearance of acetaminophen to acetaminophen cysteine and mercapturate increases with lean body weight, while the formation of these cysteine and mercapturate metabolites is also accelerated.

Besides increased CYP2E1-mediated clearance, glucuronidation and sulphation clearance are also increased in morbidly obese patients, which results in lower exposure to acetaminophen.

While a higher dose of acetaminophen may be anticipated to achieve adequate acetaminophen concentrations in morbidly obese patients, the increased CYP2E1-mediated pathway may preclude this dose adjustment.