{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:20:34Z","timestamp":1777418434030,"version":"3.51.4"},"reference-count":37,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2010,10,19]],"date-time":"2010-10-19T00:00:00Z","timestamp":1287446400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Several microtubule targeting agents are capable of inducing CYP3A4 via activation of the pregnane X receptor (PXR; NR1I2).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To evaluate the CYP3A4 induction potential of vinblastine both clinically and in vitro and determine the involvement of the nuclear receptors NR1I2 and the constitutive androstane receptor (NR1I3).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Midazolam pharmacokinetics were evaluated in 6 patients who were enrolled in a Phase 1\/2 study of infusional vinblastine given in combination with the ABCB1 (P-glycoprotein) antagonist valspodar (PSC 833) and received the CYP3A4 phenotyping probo midazolam on more than 1 occasion. Genotyping was conducted in CYP3A4, CYP3A5, and ABCB1 to rule out potential pharmacogenetic influences. Clinical data were followed-up by Western blotting and reporter assays in HepG2 and NIH3T3 cells treated with vinbfastine over a dose range of 150-4800 ng\/mL for 48 hours.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In 6 patients with cancer, vinblastine increased the median (95% CI) clearance of the CYP3A4 phenotyping probe midazolam from 21.7 L\/h (12.6 to 28.1) to 32.3 L\/h (17.3 to 53.9) (p = 0.0156, Wilcoxon signed-rank test). No obvious effect of polymorphisms in CYP3A4, CYP3A5, and ABCB1 on midazolam clearance was observed. In vitro, vinblastine induced CYP3A4 protein. Furthermore, cell-based reporter gene assays using transiently transfected HepG2 and NIH3T3 cells indicated that vinblastine (150-4800 ng\/mL) weakly activated human and mouse full-length NR1I2, but had no influence on NR1I3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Collectively, these findings suggest that vinblastine is able to induce CYP3A4, at least in part, via an NR1I2-dependent mechanism, and thus has the potential to facilitate its own elimination and cause interactions with other CYP3A4 substrates.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1345\/aph.1p354","type":"journal-article","created":{"date-parts":[[2010,10,19]],"date-time":"2010-10-19T22:40:47Z","timestamp":1287528047000},"page":"1709-1717","source":"Crossref","is-referenced-by-count":20,"title":["Induction of CYP3A4 by Vinblastine: Role of the Nuclear Receptor NR1I2"],"prefix":"10.1177","volume":"44","author":[{"given":"Nicola F","family":"Smith","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Program, Medical Oncology Branch, National Cancer Institute, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sridhar","family":"Mani","sequence":"additional","affiliation":[{"name":"Medicine and Molecular Pharmacology, Albert Einstein Cancer Center and Department of Medicine, Albert Einstein College of Medicine, Bronx, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin G","family":"Schuetz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuto","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tristan M","family":"Sissung","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Program, Medical Oncology Branch, National Cancer Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan E","family":"Bates","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics Section, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William D","family":"Figg","sequence":"additional","affiliation":[{"name":"Head of the Clinical Pharmacology Program, Medical Oncology Branch, National Cancer Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Sparreboom","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, St. Jude Children's Research 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