{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T15:10:02Z","timestamp":1751037002236,"version":"3.41.0"},"reference-count":40,"publisher":"Walter de Gruyter GmbH","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background:<\/jats:title><jats:p>For estimation of fractions metabolized (fm) by different hepatic recombinant human CYP enzymes (rhCYP), calculation of inter-system extrapolation factors (ISEFs) has been proposed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>ISEF values for CYP1A2, CYP2C19 and CYP3A4\/5 were measured. A CYP2C9 ISEF was taken from a previous report. Using a set of compounds, fractions metabolized by CYP enzymes (fm,CYP) values calculated with the ISEFs based on rhCYP data were compared with those from the chemical inhibition data. Oral pharmacokinetics (PK) profiles of midazolam were simulated using the physiologically based pharmacokinetics (PBPK) model with the CYP3A ISEF. For other CYPs, the<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>-<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>The rhCYP data with the measured ISEFs provided reasonable calculation of fm,CYP3A4 values, showing slight over-estimation compared to chemical inhibition.<\/jats:p><\/jats:sec>","DOI":"10.1515\/dmpt-2017-0024","type":"journal-article","created":{"date-parts":[[2017,11,26]],"date-time":"2017-11-26T22:15:52Z","timestamp":1511734552000},"source":"Crossref","is-referenced-by-count":0,"title":["Estimation of fractions metabolized by hepatic CYP enzymes using a concept of inter-system extrapolation factors (ISEFs) \u2013 a comparison with the chemical inhibition method"],"prefix":"10.1515","volume":"32","author":[{"given":"Ken-ichi","family":"Umehara","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Huth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilmar","family":"Schiller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tycho","family":"Heimbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Handan","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","reference":[{"key":"ref301","first-page":"1","article-title":"A comprehensive assay for nine major cytochrome P450 enzymes activities with 16 probe reactions on human liver microsomes by a single LC\/MS\/MS run to support reliable in vitro inhibitory drug\u2013drug interaction evaluation","volume":"8254","year":"2015","journal-title":"Xenobiotica"},{"key":"ref121","first-page":"687","article-title":"Abundance of cytochromes P450 in human liver: a meta-analysis","volume":"57","year":"2004","journal-title":"Br J Clin Pharmacol"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/bdd.760","article-title":"Are there differences in the catalytic activity per unit enzyme of recombinantly expressed and human liver microsomal cytochrome P450 2C9? 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