{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:39:54Z","timestamp":1790005194733,"version":"4.0.1"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2001,11,12]],"date-time":"2001-11-12T00:00:00Z","timestamp":1005523200000},"content-version":"vor","delay-in-days":195,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2001,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rifabutin is effective in the treatment and prevention of <jats:italic>Mycobacterium avium<\/jats:italic> infection in people with HIV infection. Rifabutin is structurally related to another rifamycin, rifampin, a well\u2010known inducer of the human P\u2010450 isoform 3A. The rabbit isoform CYP3A6 and the human isoform CYP3A4 have similar P\u2010450 predominance and substrate specificity and are both induced by rifampin. Our goal was to predict the CYP3A induction capacity of rifabutin and to determine if <jats:italic>ex vivo<\/jats:italic> CYP3A induction potential of rifamycins is predictive of that obtained <jats:italic>in vivo<\/jats:italic>. We determined the <jats:italic>in vivo<\/jats:italic> and <jats:italic>ex vivo<\/jats:italic> CYP3A6 induction by 4 days of treatment with rifabutin (100 mg\/kg), rifampin (100 mg\/kg), or vehicle (DMSO) in the rabbit. The <jats:italic>ex vivo<\/jats:italic> measures were CYP3A6 activity (N\u2010demethylation of erythromycin and hydroxylation of triazolam) and CYP3A content in rabbit hepatic microsomes preparations. The <jats:italic>in vivo<\/jats:italic> measures were oral clearance of triazolam and its formation clearance to its hydroxylated metabolites, <jats:italic>\u03b1<\/jats:italic>\u2010hydroxytriazolam and 4\u2010hydroxytriazolam. Rifampin increased CYP3A6 activity by 2\u2010 to 3\u2010fold in hepatic microsomes compared to vehicle. Rifabutin increased CYP3A content 1.7\u2010fold, but did not significantly increase microsomal CYP3A6 activity. Oral triazolam clearance and formation clearances to the two hydroxylated metabolites were 2\u2010 to 3\u2010fold greater in rabbits treated with rifampin. These clearances were unaffected by rifabutin administration. <jats:italic>Ex vivo<\/jats:italic> enzyme activities correlated with <jats:italic>in vivo<\/jats:italic> changes in clearance of triazolam and the formation clearance to its hydroxylated metabolites. Rifabutin is a weaker inducer of CYP3A6 than rifampin. These data suggest that <jats:italic>ex vivo<\/jats:italic> enzyme activity is a viable approach to predict <jats:italic>in vivo<\/jats:italic> inductive potential of CYP3A inducers. Copyright \u00a9 2001 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.268","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T16:22:28Z","timestamp":1030292548000},"page":"157-168","source":"Crossref","is-referenced-by-count":20,"title":["CYP3A inductive potential of the rifamycins, rifabutin and rifampin, in the rabbit"],"prefix":"10.1002","volume":"22","author":[{"given":"Allan","family":"Weber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mindy","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shazia A.","family":"Chughtai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah A.","family":"Cohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold L.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jashvant D.","family":"Unadkat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,11,12]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199309163291202"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/18.Supplement_3.S223"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.154.5.8912765"},{"key":"e_1_2_1_5_2","doi-asserted-by":"crossref","first-page":"16222","DOI":"10.1016\/S0021-9258(18)71610-4","article-title":"Regulation of the rabbit cytochrome P\u2010450 3c gene. 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