Nonalcoholic fatty liver disease (
NAFLD) is a common chronic
liver disease. The whole concept of
NAFLD has now moved into metabolic dysfunction-associated
fatty liver disease (MAFLD) to emphasize the strong metabolic derangement as the basis of the disease. Several studies have suggested that hepatic gene expression was altered in
NAFLD and
NAFLD-related metabolic comorbidities, particularly
mRNA and
protein expression of phase I and II
drug metabolism
enzymes (
DMEs).
NAFLD may affect the pharmacokinetic parameters. However, there were a limited number of pharmacokinetic studies on
NAFLD at present. Determining the pharmacokinetic variation in patients with
NAFLD remains challenging. Common modalities for modeling
NAFLD included: dietary induction, chemical induction, or genetic models. The altered expression of
DMEs has been found in rodent and human samples with
NAFLD and
NAFLD-related metabolic comorbidities. We summarized the pharmacokinetic changes of
clozapine (
CYP1A2 substrate),
caffeine (
CYP1A2 substrate),
omeprazole (
Cyp2c29/
CYP2C19 substrate),
chlorzoxazone (
CYP2E1 substrate),
midazolam (Cyp3a11/
CYP3A4 substrate) in
NAFLD. These results led us to wonder whether current
drug dosage recommendations may need to be reevaluated. More objective and rigorous studies are required to confirm these pharmacokinetic changes. We have also summarized the substrates of the
DMEs aforementioned. In conclusion,
DMEs play an important role in the metabolism of drugs. We hope that future investigations should focus on the effect and alteration of
DMEs and pharmacokinetic parameters in this special patient population with
NAFLD.