{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T21:35:14Z","timestamp":1789940114036,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,3,7]],"date-time":"2013-03-07T00:00:00Z","timestamp":1362614400000},"content-version":"vor","delay-in-days":310,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:p>Trastuzumab emtansine (T\u2010DM1) is a HER2\u2010targeted antibody\u2010drug conjugate in development for treatment of HER2\u2010positive cancers. T\u2010DM1 has been tested as a single agent in a phase I and 2 phase II studies of patients with heavily pretreated metastatic breast cancer (MBC), with the maximum tolerated dose established at 3.6 mg\/kg intravenously for every\u20103\u2010week dosing. The authors present results from the population pharmacokinetics analysis for T\u2010DM1. Population pharmacokinetics for T\u2010DM1 were characterized using a clinical database of 273 patients from the 3 studies. Pharmacokinetics was best described by a linear 2\u2010compartment model. Population estimates (interindividual variability [IIV]) for pharmacokinetic parameters were clearance, 0.7 L\/d (21.0%); central compartment volume (V<jats:sub>c<\/jats:sub>), 3.33 L (13.2%); peripheral compartment volume (V<jats:sub>p<\/jats:sub>), 0.89 L (50.4%); and intercompartmental clearance, 0.78 L\/d. Body weight, albumin, tumor burden, and aspartate aminotransferase levels were identified as statistically significant covariates accounting for interindividual variability in T\u2010DM1 pharmacokinetics, with body weight having a greater effect on IIV of clearance and V<jats:sub>c<\/jats:sub> than other covariates. T\u2010DM1 exposure was relatively consistent across the weight range following body weight\u2010based dosing. This analysis suggests no further T\u2010DM1 dose adjustments are necessary in heavily pretreated patients with MBC.<\/jats:p>","DOI":"10.1177\/0091270011403742","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T05:46:50Z","timestamp":1317188810000},"page":"691-703","source":"Crossref","is-referenced-by-count":65,"title":["Clinical Implications of Pathophysiological and Demographic Covariates on the Population Pharmacokinetics of Trastuzumab Emtansine, a HER2\u2010Targeted Antibody\u2010Drug Conjugate, in Patients With HER2\u2010Positive Metastatic Breast Cancer"],"prefix":"10.1002","volume":"52","author":[{"given":"Manish","family":"Gupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia M.","family":"LoRusso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo\u2010Hee","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Howard A.","family":"Burris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muralidhar","family":"Beeram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanu","family":"Modi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Waye","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Agresta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Klencke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amita","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandhya","family":"Girish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,7]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.9844"},{"key":"e_1_2_5_3_2","doi-asserted-by":"crossref","first-page":"9280","DOI":"10.1158\/0008-5472.CAN-08-1776","article-title":"Targeting HER2\u2010positive breast cancer with trastuzumab\u2010DM1, an antibody\u2010cytotoxic drug conjugate","volume":"6","author":"Lewis\u2010Phillips GD","year":"2008","journal-title":"Cancer Res"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.26.2071"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.29.5865"},{"key":"e_1_2_5_6_2","unstructured":"KropIE LoRussoPM MillerKD et al.A phase 2 study of the HER2 antibody\u2010drug conjugate trastuzumab\u2010DM1 (T\u2010DM1) in patients (pts) with HER2\u2010positive metastatic breast cancer (MBC) previously treated with trastuzumab lapatinib and chemotherapy. 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