Trial reportDrug metabolism and disposition: the biological fate of chemicals2011
UGT1A6 and UGT2B15 polymorphisms and acetaminophen conjugation in response to a randomized, controlled diet of select fruits and vegetables.
Trial report in Drug metabolism and disposition: the biological fate of chemicals, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 49 citations in OpenAlex.
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- CommonJournal of personalized medicine · 2022Article
- The Genomics of Elevated ALT and Adducts in Therapeutic Acetaminophen Treatment: a Pilot Study.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2021Article
- Potential role of pharmacogenomics testing in the setting of enhanced recovery pathways after surgery.Pharmacogenomics and personalized medicine · 2019Article
- Association of antioxidant nutraceuticals and acetaminophen (paracetamol): Friend or foe?Journal of food and drug analysis · 2018Review
- Race, Gender, and Genetic Polymorphism Contribute to Variability in Acetaminophen Pharmacokinetics, Metabolism, and Protein-Adduct Concentrations in Healthy African-American and European-American Volunteers.The Journal of pharmacology and experimental therapeutics · 2017Article
- Safety and pharmacokinetics of the CIME combination of drugs and their metabolites after a single oral dosing in healthy volunteers.European journal of drug metabolism and pharmacokinetics · 2016Article
- PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses.Pharmacogenetics and genomics · 2015Article
- Soybean greatly reduces valproic acid plasma concentrations: a food-drug interaction study.Scientific reports · 2014Article
- Application of physiologically based pharmacokinetic modeling to predict acetaminophen metabolism and pharmacokinetics in children.CPT: pharmacometrics & systems pharmacology · 2013Article
- Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis.Pharmaceutical research · 2013Review
- The UDP-glucuronosyltransferase (UGT) 1A polymorphism c.2042C>G (rs8330) is associated with increased human liver acetaminophen glucuronidation, increased UGT1A exon 5a/5b splice variant mRNA ratio, and decreased risk of unintentional acetaminophen-induced acute liver failure.The Journal of pharmacology and experimental therapeutics · 2013Article
- Inter-individual differences in response to dietary intervention: integrating omics platforms towards personalised dietary recommendations.The Proceedings of the Nutrition Society · 2013Article
- Mechanisms underlying food-drug interactions: inhibition of intestinal metabolism and transport.Pharmacology & therapeutics · 2012Review
- Effect of UDP-Glucuronosyltransferase (UGT) 1A Polymorphism (rs8330 and rs10929303) on Glucuronidation Status of Acetaminophen.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Acetaminophen (APAP) glucuronidation is thought to occur mainly by UDP-glucuronosyltransferases (UGT) in the UGT1A family. Interindividual variation in APAP glucuronidation is attributed in part to polymorphisms in UGT1As. However, evidence suggests that UGT2B15 may also be important. We evaluated, in a controlled feeding trial, whether APAP conjugation differed by UGT1A6 and UGT2B15 genotypes and whether supplementation of known dietary inducers of UGT (crucifers, soy, and citrus) modulated APAP glucuronidation compared with a diet devoid of fruits and vegetables (F&V). Healthy adults (n = 66) received 1000 mg of APAP orally on days 7 and 14 of each 2-week feeding period and collected saliva and urine over 12 h. Urinary recovery of the percentage of the APAP dose as free APAP was higher (P = 0.02), and the percentage as APAP glucuronide (APAPG) was lower (P = 0.004) in women. The percentage of APAP was higher among UGT1A6*1/*1 genotypes, relative to *1/*2 and *2/*2 genotypes (P = 0.045). For UGT2B15, the percentage of APAPG decreased (P < 0.0001) and that of APAP sulfate increased (P = 0.002) in an allelic dose-dependent manner across genotypes from *1/*1 to *2/*2. There was a significant diet × UGT2B15 genotype interaction for the APAPG ratio (APAPG/total metabolites × 100) (P = 0.03), with *1/*1 genotypes having an approximately 2-fold higher F&V to basal diet difference in response compared with *1/*2 and *2/*2 genotypes. Salivary APAP maximum concentration (C(max)) was significantly higher in women (P = 0.0003), with F&V (P = 0.003), and among UGT1A6*2/*2 and UGT2B15*1/*2 genotypes (P = 0.02 and 0.002, respectively). APAP half-life was longer in UGT2B15*2/*2 genotypes with F&V (P = 0.009). APAP glucuronidation was significantly influenced by the UGT2B15*2 polymorphism, supporting a role in vivo for UGT2B15 in APAP glucuronidation, whereas the contribution of UGT1A6*2 was modest. Selected F&V known to affect UGT activity led to greater glucuronidation and less sulfation.
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