Common UGT1A6 Variant Alleles Determine Acetaminophen Pharmacokinetics in Man.

ABSTRACT: Acetaminophen (paracetamol) is a widely used drug that causes adverse drug events that are often dose-dependent and related to plasma drug concentrations. Acetaminophen metabolism strongly depends on UGT1A enzymes. We aimed to investigate putative factors influencing acetaminophen pharmacokinetics. We analyzed acetaminophen pharmacokinetics after intravenous administration in 186 individuals, and we determined the effect of sex; body mass index (BMI); previous and concomitant therapy with UGT1A substrates, inhibitors, and inducers; as well as common variations in the genes coding for UGT1A1, UGT1A6, and UGT1A9. We identified sex and UGT1A6 genetic variants as major factors influencing acetaminophen pharmacokinetics, with women showing lower clearance (p < 0.001) and higher area under the p

SUBMITTER: Cerezo-Arias MLO 

PROVIDER: S-EPMC9143054 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature