{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T04:07:50Z","timestamp":1747109270730,"version":"3.40.5"},"reference-count":60,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["dmd.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Metabolism and Disposition"],"published-print":{"date-parts":[[2025,2]]},"DOI":"10.1016\/j.dmd.2024.100030","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T06:25:16Z","timestamp":1733984716000},"page":"100030","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Improvement in static and dynamic projections of drug-drug interactions caused by cytochrome P4503A time-dependent inhibitors through in\u00a0vitro allosteric modulation by progesterone"],"prefix":"10.1016","volume":"53","author":[{"given":"Pooja","family":"Hegde","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brianna","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alec","family":"Bell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen D.","family":"Hall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc R.A.","family":"Roug\u00e9e","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1124\/dmd.112.044644","article-title":"Time-dependent inhibition and estimation of CYP3A clinical pharmacokinetic drug-drug interactions using plated human cell systems","volume":"40","author":"D R Albaugh","year":"2012","journal-title":"Drug Metab Dispos"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1124\/dmd.30.12.1497","article-title":"The influence of nonspecific microsomal binding on apparent intrinsic clearance, and its prediction from physicochemical properties","volume":"30","author":"R P Austin","year":"2002","journal-title":"Drug Metab Dispos"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/BF00196114","article-title":"A pharmacokinetic interaction between roxithromycin and midazolam","volume":"46","author":"J T Backman","year":"1994","journal-title":"Eur J Clin Pharmacol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/psp4.12449","article-title":"Recommendations for the design of clinical drugedrug interaction studies with itraconazole using a mechanistic physiologically-based pharmacokinetic model","volume":"8","author":"Y Chen","year":"2019","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"ref5","doi-asserted-by":"crossref","DOI":"10.1517\/17425250802500028","article-title":"Allosteric P450 mechanisms: multiple binding sites, multiple conformers or both?","volume":"4","author":"D R Davydov","year":"2008","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"7066","DOI":"10.1074\/jbc.M609589200","article-title":"Cooperativity in cytochrome P450 3A4: linkages in substrate binding, spin state, uncoupling, and product formation","volume":"282","author":"I G Denisov","year":"2007","journal-title":"J Biol Chem"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.pharmthera.2009.05.011","article-title":"Cooperative properties of cytochromes P450","volume":"124","author":"I G Denisov","year":"2009","journal-title":"Pharmacol Ther"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1021\/acs.biochem.5b00079","article-title":"Mechanism of drug-drug interactions mediated by human cytochrome P450 CYP3A4 monomer","volume":"54","author":"I G Denisov","year":"2015","journal-title":"Biochemistry"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1021\/acs.biochem.8b01268","article-title":"Allosteric interactions in human cytochrome P450 CYP3A4: the role of phenylalanine 213","volume":"58","author":"I G Denisov","year":"2019","journal-title":"Biochemistry"},{"key":"ref10","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics12090846","article-title":"Mechanisms of CYP450 inhibition: understanding drug-drug interactions due to mechanism-based inhibition in clinical practice","volume":"12","author":"M Deodhar","year":"2020","journal-title":"Pharmaceutics"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1080\/17425255.2021.1935866","article-title":"Evolving approaches on measurements and applications of intracellular free drug concentration and Kpuu in drug discovery","volume":"17","author":"L Di","year":"2021","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1021\/acs.bioconjchem.9b00248","article-title":"A covalently attached progesterone molecule outcompetes the binding of free progesterone at an allosteric site of cytochrome P450 3A4","volume":"30","author":"J Ducharme","year":"2019","journal-title":"Bioconjug Chem"},{"key":"ref13","article-title":"Cytochrome P450 3A time-dependent inhibition assays are too sensitive for identification of drugs causing clinically significant drug-drug interactions: a comparison of human liver microsomes and hepatocytes and definition of boundaries for inactivation rate constants","volume":"49","author":"H Eng","year":"2021","journal-title":"Drug Metab Dispos"},{"year":"2020","author":"Fda","journal-title":"Vitro Drug Interaction StudiesdCytochrome P450 Enzyme-And Transporter-Mediated Drug Interactions Guidance for Industry. US Food and Drug Administration","key":"ref14"},{"key":"ref15","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-42051-x","article-title":"Improved predictions of time-dependent drug-drug interactions by determination of cytosolic drug concentrations","volume":"9","author":"A M Filppula","year":"2019","journal-title":"Sci Rep"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2174\/138920006776359293","article-title":"A critical evaluation of the experimental design of studies of mechanism based enzyme inhibition, with implications for in vitroin vivo extrapolation","volume":"7","author":"F Ghanbari","year":"2006","journal-title":"Curr Drug Metab"},{"key":"ref17","doi-asserted-by":"crossref","DOI":"10.1124\/dmd.109.026716","article-title":"The conduct of in vitro studies to address timedependent inhibition of drug-metabolizing enzymes: a perspective of the pharmaceutical research and manufacturers of America","volume":"37","author":"S W Grimm","year":"2009","journal-title":"Drug Metab Dispos"},{"key":"ref18","doi-asserted-by":"crossref","DOI":"10.1124\/dmd.110.036103","article-title":"Critique of the two-fold measure of prediction success for ratios: application for the assessment of drug-drug interactions","volume":"39","author":"E J Guest","year":"2011","journal-title":"Drug Metab Dispos"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1007\/s00204-020-02936-7","article-title":"Inhibition and induction of CYP enzymes in humans: an update","volume":"94","author":"J Hakkola","year":"2020","journal-title":"Arch Toxicol"},{"author":"N Hanke","key":"ref20"},{"volume":"12","journal-title":"Pharmaceutics","article-title":"A mechanistic, enantioselective, physiologically based pharmacokinetic model of verapamil and norverapamil, built and evaluated for drug-drug interaction studies","key":"ref21"},{"key":"ref22","doi-asserted-by":"crossref","DOI":"10.1124\/dmd.108.021279","article-title":"Comparative analysis of CYP3A heteroactivation by steroid hormones and flavonoids in different in vitro systems and potential in vivo implications","volume":"36","author":"J Henshall","year":"2008","journal-title":"Drug Metab Dispos"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1007\/s00216-008-2244-0","article-title":"Substrate binding to cytochromes P450","volume":"392","author":"E M Isin","year":"2008","journal-title":"Anal Bioanal Chem"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1124\/dmd.104.000315","article-title":"Role of itraconazole metabolites in CYP3A4 inhibition","volume":"32","author":"N Isoherranen","year":"2004","journal-title":"Drug Metab Dispos"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1002\/jcph.495","article-title":"Clinical drug interaction profile of idelalisib in healthy subjects","volume":"55","author":"F Jin","year":"2015","journal-title":"J Clin Pharmacol"},{"year":"2008","author":"P Kang","journal-title":"CYP3A4mediated carbamazepine (CBZ) metabolism: formation of a covalent CBZ-CYP3A4 adduct and alteration of the enzyme kinetic profile","key":"ref26"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.1016\/j.xphs.2017.04.077","article-title":"Risk assessment using cytochrome P450 time-dependent inhibition assays at single time and concentration in the early stage of drug discovery","volume":"106","author":"M Kosaka","year":"2017","journal-title":"J Pharm Sci"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1124\/dmd.111.043158","article-title":"Predictions of cytochrome P450-mediated drug-drug interactions using cryopreserved human hepatocytes: comparison of plasma and protein-free media incubation conditions","volume":"40","author":"J Mao","year":"2012","journal-title":"Drug Metab Dispos"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/978-1-62703-758-7_5","article-title":"Irreversible enzyme inhibition kinetics and drugdrug interactions","volume":"1113","author":"M Mohutsky","year":"2014","journal-title":"Methods Mol Biol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1124\/dmd.30.5.534","article-title":"Effects of endogenous steroids on CYP3A4-mediated drug metabolism by human liver microsomes","volume":"30","author":"H Nakamura","year":"2002","journal-title":"Drug Metab Dispos"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1124\/dmd.31.4.432","article-title":"CYP3A4 and CYP3A7-mediated carbamazepine 10, 11-epoxidation are activated by differential endogenous steroids","volume":"31","author":"H Nakamura","year":"2003","journal-title":"Drug Metab Dispos"},{"key":"ref32","doi-asserted-by":"crossref","DOI":"10.1124\/jpet.105.093229","article-title":"The utility of in vitro cytochrome P450 inhibition data in the prediction of drug-drug interactions","volume":"316","author":"R S Obach","year":"2006","journal-title":"J Pharmacol Exp Ther"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1124\/dmd.106.012633","article-title":"Mechanism-based inactivation of human cytochrome p450 enzymes and the prediction of drug-drug interactions","volume":"35","author":"R S Obach","year":"2007","journal-title":"Drug Metab Dispos"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrd1506","article-title":"Small but significant","volume":"3","author":"J Owens","year":"2004","journal-title":"Nat Rev Drug Discov"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1124\/dmd.111.038596","article-title":"An evaluation of the dilution method for identifying metabolism-dependent inhibitors of cytochrome P450 enzymes","volume":"39","author":"A Parkinson","year":"2011","journal-title":"Drug Metab Dispos"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1021\/acs.bioconjchem.6b00604","article-title":"Allosteric activation of cytochrome P450 3A4 via progesterone bioconjugation","volume":"28","author":"V Polic","year":"2017","journal-title":"Bioconjug Chem"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/cld.10","article-title":"Managing drug-drug interactions with boceprevir and telaprevir","volume":"1","author":"A S Rangnekar","year":"2012","journal-title":"Clin Liver Dis (Hoboken)"},{"key":"ref38","article-title":"Impact of heterotropic allosteric modulation on the time-dependent inhibition of cytochrome P450 3A4","volume":"51","author":"Lra Roug Ee","year":"2023","journal-title":"Drug Metab Dispos"},{"key":"ref39","article-title":"Heterotropic allosteric modulation of CYP3A4 in vitro by progesterone: evidence for improvement in prediction of time dependent inhibition for macrolides","author":"Lra Roug Ee","year":"2025","journal-title":"Drug Metab Dispos"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ejps.2011.04.008","article-title":"Prediction of time-dependent CYP3A4 drug-drug interactions by physiologically based pharmacokinetic modelling: impact of inactivation parameters and enzyme turnover","volume":"43","author":"K Rowland-Yeo","year":"2011","journal-title":"Eur J Pharm Sci"},{"key":"ref41","doi-asserted-by":"crossref","DOI":"10.3390\/ijms232012591","article-title":"Crystal structure of CYP3A4 complexed with fluorol identifies the substrate access channel as a high-affinity ligand binding site","volume":"23","author":"I F Sevrioukova","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/0076-6879(95)49038-8","article-title":"Mechanism-based enzyme inactivators","volume":"249","author":"R B Silverman","year":"1995","journal-title":"Methods Enzymol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"637","DOI":"10.3109\/00498254.2010.500407","article-title":"Evaluation of the human prediction of clearance from hepatocyte and microsome intrinsic clearance for 52 drug compounds","volume":"40","author":"A K Sohlenius-Sternbeck","year":"2010","journal-title":"Xenobiotica"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1517\/17425255.2014.856882","article-title":"Exploring concepts of in vitro time-dependent CYP inhibition assays","volume":"10","author":"D M Stresser","year":"2014","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"ref45","doi-asserted-by":"crossref","DOI":"10.1016\/j.dmd.2024.100030","volume":"53","author":"P Hegde","year":"2025","journal-title":"Drug Metabolism and Disposition"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/S0022-3565(24)36788-6","article-title":"Role of CYP3A4 in human hepatic diltiazem N-demethylation: inhibition of CYP3A4 activity by oxidized diltiazem metabolites","volume":"282","author":"D Sutton","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1111\/bcp.13953","article-title":"Erlotinib treatment induces cytochrome P450 3A activity in non-small cell lung cancer patients","volume":"85","author":"A Svedberg","year":"2019","journal-title":"Br J Clin Pharmacol"},{"key":"ref48","doi-asserted-by":"crossref","DOI":"10.1124\/dmd.121.000497","article-title":"Static and dynamic projections of drug-drug interactions caused by cytochrome P450 3A time-dependent inhibitors measured in human liver microsomes and hepatocytes","volume":"49","author":"E Tseng","year":"2021","journal-title":"Drug Metab Dispos"},{"key":"ref49","doi-asserted-by":"crossref","DOI":"10.1002\/bmc.4511","article-title":"Simultaneous determination of idelalisib and its metabolite GS-563117 in dog plasma by LCeMS\/MS: application to a pharmacokinetic study","volume":"33","author":"C Wang","year":"2019","journal-title":"Biomed Chromatogr"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1126\/science.1099736","article-title":"Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone","volume":"305","author":"P A Williams","year":"2004","journal-title":"Science"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"4077","DOI":"10.1021\/acs.molpharmaceut.9b00525","article-title":"Prediction of fraction unbound in microsomal and hepatocyte incubations: a comparison of methods across industry datasets","volume":"16","author":"S Winiwarter","year":"2019","journal-title":"Mol Pharm"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s10822-015-9836-5","article-title":"Time dependent analysis of assay comparability: a novel approach to understand intra-and inter-site variability over time","volume":"29","author":"S Winiwarter","year":"2015","journal-title":"J Comput Aided Mol Des"},{"key":"ref53","doi-asserted-by":"crossref","DOI":"10.1021\/acs.molpharmaceut.8b00129","article-title":"Improved predictions of drug-drug interactions mediated by time-dependent inhibition of CYP3A","volume":"15","author":"J Yadav","year":"2018","journal-title":"Mol Pharm"},{"key":"ref54","article-title":"Time-dependent enzyme inactivation: Numerical analyses of in vitro data and prediction of drug-drug interactions","volume":"206","author":"J Yadav","journal-title":"Pharmacol Ther"},{"key":"ref55","first-page":"1053","article-title":"Comparative studies of in vitro inhibition of cytochrome P450 3A4-dependent testosterone 6beta-hydroxylation by roxithromycin and its metabolites, troleandomycin, and erythromycin","volume":"26","author":"H Yamazaki","year":"1998","journal-title":"Drug Metab Dispos"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1080\/00498250210158230","article-title":"Reversible and irreversible inhibition of CYP3A enzymes by tamoxifen and metabolites","volume":"32","author":"X J Zhao","year":"2002","journal-title":"Xenobiotica"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"415","DOI":"10.2174\/1389200043335450","article-title":"Therapeutic drugs that behave as mechanism-based inhibitors of cytochrome P450 3A4","volume":"5","author":"S Zhou","year":"2004","journal-title":"Curr Drug Metab"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1021\/acs.chemrestox.8b00023","article-title":"Identification of novel pathways in idelalisib metabolism and bioactivation","volume":"31","author":"J Zhu","year":"2018","journal-title":"Chem Res Toxicol"},{"key":"ref59","doi-asserted-by":"crossref","DOI":"10.1124\/dmd.110.037911","article-title":"CYP3A time-dependent inhibition risk assessment validated with 400 reference drugs","volume":"39","author":"A Zimmerlin","year":"2011","journal-title":"Drug Metab Dispos"},{"key":"ref60","doi-asserted-by":"crossref","DOI":"10.1016\/j.dmd.2024.100030","volume":"53","author":"P Hegde","year":"2025","journal-title":"Drug Metabolism and Disposition"}],"container-title":["Drug Metabolism and Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955624158801?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955624158801?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T20:38:45Z","timestamp":1747082325000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0090955624158801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":60,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["S0090955624158801"],"URL":"https:\/\/doi.org\/10.1016\/j.dmd.2024.100030","relation":{},"ISSN":["0090-9556"],"issn-type":[{"type":"print","value":"0090-9556"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Improvement in static and dynamic projections of drug-drug interactions caused by cytochrome P4503A time-dependent inhibitors through in\u00a0vitro allosteric modulation by progesterone","name":"articletitle","label":"Article Title"},{"value":"Drug Metabolism and Disposition","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.dmd.2024.100030","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 American Society for Pharmacology and Experimental Therapeutics. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"100030"}}