{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T11:12:40Z","timestamp":1761045160448,"version":"build-2065373602"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:00:00Z","timestamp":1325808000000},"content-version":"vor","delay-in-days":704,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:p><jats:bold>Study Objective.<\/jats:bold> To examine the effect of telavancin, a lipoglycopeptide antibiotic with potent gram\u2010positive activity, on the pharmacokinetics of midazolam, a cytochrome P450 (CYP) 3A probe substrate.<\/jats:p><jats:p><jats:bold>Design.<\/jats:bold> Phase I, randomized, double\u2010blind, placebo\u2010controlled, crossover study<\/jats:p><jats:p><jats:bold>Setting.<\/jats:bold> Clinical research center.<\/jats:p><jats:p><jats:bold>Participants.<\/jats:bold> Sixteen healthy adult volunteers.<\/jats:p><jats:p><jats:bold>Intervention.<\/jats:bold> Subjects were randomly assigned to receive an intravenous infusion of telavancin 10 mg\/kg or placebo once\/day for 7 days. On day 7, a single dose of intravenous midazolam 1 mg was given immediately after completion of the last infusion of telavancin or placebo. Patients crossed over to the alternate treatment regimen after a washout period of at least 7 days.<\/jats:p><jats:p><jats:bold>Measurements and Main Results.<\/jats:bold> Pharmacokinetic sampling was performed on study days 7 and 21. Blood was collected before telavancin or placebo dosing and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after midazolam administration. Formal equivalence analysis using the two onesided <jats:italic>t<\/jats:italic> test method showed that the geometric mean ratios for maximum plasma concentration (C<jats:sub>max<\/jats:sub>) and areas under the plasma concentrationtime curve (AUC) for midazolam coadministered with telavancin versus midazolam coadministered with placebo were close to unity. The 90% confidence intervals (CIs) around the ratios fell within the 0.8\u20101.25 bioequivalence bounds (geometric mean ratio for AUC from time zero to the last measured plasma concentration 0.95, 90% CI 0.910\u20100.984; C<jats:sub>max<\/jats:sub> geometric mean ratio 1.03, 90% CI 0.956\u20101.11). The multiple\u2010dose pharmacokinetic profile of telavancin with concomitant administration of midazolam (C<jats:sub>max<\/jats:sub> 97 \u03bcg\/ml, concentration 24 hrs after completion of telavancin infusion 9 \u03bcg\/ml, terminal\u2010phase elimination half\u2010life 8.9 hrs, clearance 13.3 ml\/hr\/kg) was consistent with data from earlier studies.<\/jats:p><jats:p><jats:bold>Conclusion.<\/jats:bold> These pharmacokinetic data show that intravenous telavancin administered at the intended therapeutic dose does not affect the pharmacokinetics of intravenous midazolam. The results indicate that telavancin is unlikely to inhibit hepatic CYP3A activity to a clinically meaningful extent.<\/jats:p>","DOI":"10.1592\/phco.30.2.136","type":"journal-article","created":{"date-parts":[[2010,1,26]],"date-time":"2010-01-26T07:58:26Z","timestamp":1264492706000},"page":"136-143","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Effect of Telavancin on the Pharmacokinetics of the Cytochrome P450 3A Probe Substrate Midazolam: A Randomized, Double\u2010Blind, Crossover Study in Healthy Subjects"],"prefix":"10.1002","volume":"30","author":[{"given":"Shekman L.","family":"Wong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R.","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles H.","family":"Ballow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael M.","family":"Kitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven L.","family":"Barriere","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,1,6]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.11.3602-3604.2003"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.57.326"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl424"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl235"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00100-07"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh156"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.6.2149-2152.2004"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.3.1127-1134.2005"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/429914"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.3.862-867.2006"},{"issue":"7","key":"e_1_2_1_12_2","first-page":"S14","article-title":"Telavancin for hospital\u2010acquired pneumonia, including ventilator\u2010associated pneumonia: the ATTAIN studies [abstract]","volume":"14","author":"Rubinstein E","year":"2008","journal-title":"Clin Microbiol Infect"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/587896"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.1.195-201.2005"},{"volume-title":"Data on file","year":"2006","author":"Theravance, Inc.","key":"e_1_2_1_15_2"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.31.7.815"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010994022294"},{"volume-title":"Drug development and drug interactions: table of substrates, inhibitors and inducers","year":"2006","author":"Center for Drug Evaluation and Research.","key":"e_1_2_1_18_2"},{"volume-title":"Guidance for industry. Bioavailability and bioequivalence studies for orally administered drug products\u2014general considerations","year":"2003","author":"Center for Drug Evaluation and Research.","key":"e_1_2_1_19_2"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-0520"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1592%2Fphco.30.2.136","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1592\/phco.30.2.136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T10:29:17Z","timestamp":1761042557000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1592\/phco.30.2.136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,2]]},"references-count":19,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2010,2]]}},"alternative-id":["10.1592\/phco.30.2.136"],"URL":"https:\/\/doi.org\/10.1592\/phco.30.2.136","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"type":"print","value":"0277-0008"},{"type":"electronic","value":"1875-9114"}],"subject":[],"published":{"date-parts":[[2010,2]]},"assertion":[{"value":"2012-01-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}