{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:30:12Z","timestamp":1791329412805,"version":"4.3.1"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,2,2]],"date-time":"2006-02-02T00:00:00Z","timestamp":1138838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Using the fluconazole\u2013zidovudine (AZT) interaction as a model, to determine whether inhibition of UDP\u2013glucuronosyltransferase (UGT) catalysed drug metabolism<jats:italic>in vivo<\/jats:italic>could be predicted quantitatively from<jats:italic>in vitro<\/jats:italic>kinetic data generated in the presence and absence bovine serum albumin (BSA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Kinetic 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.<jats:italic>K<\/jats:italic><jats:sub><jats:italic>i<\/jats:italic><\/jats:sub>values were used to estimate the decrease in AZT clearance<jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Addition of BSA (2%) to incubations decreased the<jats:italic>K<\/jats:italic><jats:sub><jats:italic>m<\/jats:italic><\/jats:sub>values for AZT glucuronidation by 85\u201390% for the HLM (923\u2003\u00b1\u2003357 to 91\u2003\u00b1\u20039\u2003\u00b5<jats:sc>m<\/jats:sc>) and UGT2B7 (478\u201370\u2003\u00b5<jats:sc>m<\/jats:sc>) catalysed reactions, with little effect on<jats:italic>V<\/jats:italic><jats:sub>max<\/jats:sub>. Fluconazole, which was shown to be a selective inhibitor of UGT2B7, competitively inhibited AZT glucuronidation by HLM and UGT2B7. Like the<jats:italic>K<\/jats:italic><jats:sub><jats:italic>m<\/jats:italic><\/jats:sub>, BSA caused an 87% reduction in the<jats:italic>K<\/jats:italic><jats:sub><jats:italic>i<\/jats:italic><\/jats:sub>for fluconazole inhibition of AZT glucuronidation by HLM (1133\u2003\u00b1\u2003403 to 145\u2003\u00b1\u200336\u2003\u00b5<jats:sc>m<\/jats:sc>) and UGT2B7 (529 to 73\u2003\u00b5<jats:sc>m<\/jats:sc>).<jats:italic>K<\/jats:italic><jats:sub><jats:italic>i<\/jats:italic><\/jats:sub>values determined for fluconazole using HLM and UGT2B7 in the presence (but not absence) of BSA predicted an interaction<jats:italic>in vivo<\/jats:italic>. The predicted magnitude of the interaction ranged from 41% to 217% of the reported AUC increase in patients, depending on the value of the<jats:italic>in vivo<\/jats:italic>fluconazole concentration employed in calculations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>K<\/jats:italic><jats:sub><jats:italic>i<\/jats:italic><\/jats:sub>values determined under certain experimental conditions may quantitatively predict inhibition of UGT catalysed drug glucuronidation<jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2006.02588.x","type":"journal-article","created":{"date-parts":[[2006,2,2]],"date-time":"2006-02-02T14:29:00Z","timestamp":1138890540000},"page":"427-439","source":"Crossref","is-referenced-by-count":162,"title":["Quantitative prediction of<i>in vivo<\/i>inhibitory interactions involving glucuronidated drugs from<i>in vitro<\/i>data: the effect of fluconazole on zidovudine 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