{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:18:17Z","timestamp":1782793097877,"version":"3.54.5"},"reference-count":15,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"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":[[2006,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Lasofoxifene, a selective estrogen receptor modulator, may be coadministered with other drugs, raising the issue of drug\u2013drug interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Using a 7-day, open-label, sequential study to determine whether lasofoxifene at steady-state concentration affects cytochrome P450\u2013mediated drug metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Lasofoxifene was tested in 18 postmenopausal women with probe drugs for CYP2E1 and CYP2D6. Changes in CYP2E1 metabolism were measured by the formation clearance of 6-hydroxychlorzoxazone (6-OHCLZ; Cl\n                      <jats:sub>f,6-OHCLZ<\/jats:sub>\n                      ) following a 250 mg dose of chlorzoxazone in the absence (day 1) and presence (day 6) of lasofoxifene. Changes in the dextromethorphan\/dextrorphan urine metabolic ratio (MRDX) measured the effect on CYP2D6 metabolism following a 30 mg dose of dextromethorphan in the absence and presence of lasofoxifene (days 2 and 7).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Steady-state lasofoxifene did not affect the formation clearance of 6-OHCLZ or the urinary MRDX. For 6-OHCLZ, the lower boundary (87.12%) of the 90% confidence interval for the ratio (day 6\/day 1) of Cl\n                      <jats:sub>f,6-OHCLZ<\/jats:sub>\n                      was well above the clinically acceptable ratio of 60%. Both the individual and group mean Cl\n                      <jats:sub>f,6-OHCLZ<\/jats:sub>\n                      values were comparable in the absence and presence of lasofoxifene. For MRDX, the upper boundary (129.37%) of the 90% confidence interval for the ratio (day 7\/day 2) of MRDX was well below the stipulated ratio of 200%. The individual and mean MRDX values were comparable in the absence and presence of lasofoxifene. Lasofoxifene was well tolerated; adverse events were mild and transient.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Lasofoxifene has no effect on CYP2E1- or CYP2D6-mediated drug metabolism and should not affect drugs metabolized by other cytochrome P450 isoenzymes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1345\/aph.1g347","type":"journal-article","created":{"date-parts":[[2005,12,20]],"date-time":"2005-12-20T21:28:18Z","timestamp":1135114098000},"page":"32-37","source":"Crossref","is-referenced-by-count":10,"title":["Effects of Steady-State Lasofoxifene on Cyp2D6- and Cyp2E1-Mediated Metabolism"],"prefix":"10.1177","volume":"40","author":[{"given":"Robert A","family":"Moller","sequence":"first","affiliation":[{"name":"Pfizer Worldwide Clinical Development, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannine M","family":"Fisher","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development, Groton, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann E","family":"Taylor","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheela","family":"Kolluri","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J","family":"Gardner","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Scott","family":"Obach","sequence":"additional","affiliation":[{"name":"Pharmacokinetics, Dynamics, and Drug Metabolism, Pfizer Global Research and Development"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L","family":"Walsky","sequence":"additional","affiliation":[{"name":"Pharmacokinetics, Dynamics, and Drug Metabolism, Pfizer Global Research and Development"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2006,1,1]]},"reference":[{"key":"bibr1-aph.1G347","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022219"},{"key":"bibr2-aph.1G347","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.3.321"},{"key":"bibr3-aph.1G347","doi-asserted-by":"publisher","DOI":"10.1016\/S1040-8428(02)00022-7"},{"key":"bibr4-aph.1G347","first-page":"8683","volume":"61","author":"Cohen LA","year":"2001","journal-title":"Cancer Res"},{"key":"bibr5-aph.1G347","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.4.5902"},{"key":"bibr6-aph.1G347","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-1481"},{"key":"bibr7-aph.1G347","first-page":"S93","volume":"32","author":"Bolognese M","year":"2003","journal-title":"Bone"},{"key":"bibr8-aph.1G347","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2002.01522.x"},{"key":"bibr9-aph.1G347","doi-asserted-by":"publisher","DOI":"10.1592\/phco.22.12.1001.33603"},{"key":"bibr10-aph.1G347","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.32.6.647"},{"key":"bibr11-aph.1G347","doi-asserted-by":"publisher","DOI":"10.1007\/BF01771666"},{"key":"bibr12-aph.1G347","doi-asserted-by":"publisher","DOI":"10.1097\/00000421-199112002-00004"},{"key":"bibr13-aph.1G347","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-2115(98)00278-4"},{"key":"bibr14-aph.1G347","doi-asserted-by":"publisher","DOI":"10.1021\/jm980048b"},{"key":"bibr15-aph.1G347","first-page":"6","author":"Moller R","year":"2004","journal-title":"AAPSJ"}],"container-title":["Annals of Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1345\/aph.1G347","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1345\/aph.1G347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:11:22Z","timestamp":1777374682000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1345\/aph.1G347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,1]]}},"alternative-id":["10.1345\/aph.1G347"],"URL":"https:\/\/doi.org\/10.1345\/aph.1g347","relation":{},"ISSN":["1060-0280","1542-6270"],"issn-type":[{"value":"1060-0280","type":"print"},{"value":"1542-6270","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,1]]}}}