ArticleBritish journal of clinical pharmacology2006
Quantitative prediction of in vivo inhibitory interactions involving glucuronidated drugs from in vitro data: the effect of fluconazole on zidovudine glucuronidation.
Article in British journal of clinical pharmacology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 176 citations in OpenAlex.
- Population pharmacokinetics of unbound mycophenolic acid in adult allogeneic haematopoietic cell transplantation: effect of pharmacogenetic factors.British journal of clinical pharmacology · 2013Pooled it
- UGTformer: a pretrained graph transformer model for predicting UDP-glucuronosyltransferase-mediated drug metabolism.Journal of cheminformatics · 2026Article
- Physiologically based pharmacokinetic modeling of fluconazole: interpretation of gender-dependent pharmacokinetics and cytochrome P450 inhibition.Frontiers in pharmacology · 2026Article
- Predicting in vivo cannabinoid-drug interactions mediated via inhibition of UDP-glucuronosyltransferases using in vitro studies and physiologically based pharmacokinetic modeling and simulations.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- UGT2B10 is the Major UDP-Glucuronosyltransferase 2B Isoform Involved in the Metabolism of Lamotrigine and is Implicated in the Drug-Drug Interaction with Valproic Acid.The AAPS journal · 2024Article
- Article
- Enzyme Kinetics of Uridine Diphosphate Glucuronosyltransferases (UGTs).Methods in molecular biology (Clifton, N.J.) · 2021Article
- Reviewing Data Integrated for PBPK Model Development to Predict Metabolic Drug-Drug Interactions: Shifting Perspectives and Emerging Trends.Frontiers in pharmacology · 2021Review
- Article
- Influence of Stereochemistry on the Bioactivation and Glucuronidation of 4-Ipomeanol.The Journal of pharmacology and experimental therapeutics · 2019Article
- Oral Coadministration of Fluconazole with Tramadol Markedly Increases Plasma and Urine Concentrations of Tramadol and theDrug metabolism and disposition: the biological fate of chemicals · 2019Article
- Inhibition of UGT2B7 Enzyme Activity in Human and Rat Liver Microsomes by Herbal Constituents.Molecules (Basel, Switzerland) · 2018Article
- Inhibitory Effect of Sauchinone on UDP-Glucuronosyltransferase (UGT) 2B7 Activity.Molecules (Basel, Switzerland) · 2018Article
- Physiologically based pharmacokinetic modeling of disposition and drug-drug interactions for valproic acid and divalproex.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2018Article
- In Vitro Inhibition of Human UDP-Glucuronosyl-Transferase (UGT) Isoforms by Astaxanthin, β-Cryptoxanthin, Canthaxanthin, Lutein, and Zeaxanthin: Prediction of in Vivo Dietary Supplement-Drug Interactions.Molecules (Basel, Switzerland) · 2016Article
- Article
- Placental profiling of UGT1A enzyme expression and activity and interactions with preeclampsia at term.European journal of drug metabolism and pharmacokinetics · 2015Article
- Tissue and species differences in the glucuronidation of glabridin with UDP-glucuronosyltransferases.Chemico-biological interactions · 2015Article
- Identifying and applying a highly selective probe to simultaneously determine the O-glucuronidation activity of human UGT1A3 and UGT1A4.Scientific reports · 2015Article
- Inhibition of human drug-metabolising cytochrome P450 and UDP-glucuronosyltransferase enzyme activities in vitro by uremic toxins.European journal of clinical pharmacology · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsUsing the fluconazole-zidovudine (AZT) interaction as a model, to determine whether inhibition of UDP-glucuronosyltransferase (UGT) catalysed drug metabolism in vivo could be predicted quantitatively from in vitro kinetic data generated in the presence and absence bovine serum albumin (BSA).
methodsKinetic constants for AZT glucuronidation were generated using human liver microsomes (HLM) and recombinant UGT2B7, the principal enzyme responsible for AZT glucuronidation, as the enzyme sources with and without fluconazole. K(i) values were used to estimate the decrease in AZT clearance in vivo.
resultsAddition of BSA (2%) to incubations decreased the K(m) values for AZT glucuronidation by 85-90% for the HLM (923 +/- 357 to 91 +/- 9 microm) and UGT2B7 (478-70 microm) catalysed reactions, with little effect on V(max). Fluconazole, which was shown to be a selective inhibitor of UGT2B7, competitively inhibited AZT glucuronidation by HLM and UGT2B7. Like the K(m), BSA caused an 87% reduction in the K(i) for fluconazole inhibition of AZT glucuronidation by HLM (1133 +/- 403 to 145 +/- 36 microm) and UGT2B7 (529 to 73 microm). K(i) values determined for fluconazole using HLM and UGT2B7 in the presence (but not absence) of BSA predicted an interaction in vivo. The predicted magnitude of the interaction ranged from 41% to 217% of the reported AUC increase in patients, depending on the value of the in vivo fluconazole concentration employed in calculations.
conclusionsK(i) values determined under certain experimental conditions may quantitatively predict inhibition of UGT catalysed drug glucuronidation in vivo.
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