{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:34:57Z","timestamp":1791480897292,"version":"4.3.4"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>We studied the pharmacokinetics and exposure\u2013response relationships of the brentuximab vedotin (BV) antibody\u2013drug conjugate (ADC) and unconjugated monomethyl auristatin E in haematologic malignancies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This population pharmacokinetic analysis included data from five adult and three paediatric studies. Exposures in virtual adult and paediatric populations following BV 1.8 mg\/kg (maximum 180 mg) intravenously every 3 weeks were simulated. Clinical endpoints included overall response rate, grade \u22652 peripheral neuropathy (PN) and grade \u22653 neutropenia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BV ADC exhibited linear pharmacokinetics, well\u2010described by a three\u2010compartment model, with body weight being the only significant covariate for exposure. Monomethyl auristatin E exhibited time\u2010varying formation rate. Simulated steady\u2010state BV ADC exposures in patients aged 12 to &lt;18 years were similar to those of adult patients, but 23%\u201338% lower in patients aged 2 to &lt;12 years. Despite lower exposure, clinical activity was observed with BV 1.8 mg\/kg every 3 weeks in those aged 2 to &lt;12 years (overall response rate: 2 to &lt;12 years, 60%; 12 to &lt;18 years, 43%). In adult, but not paediatric patients, increased BV ADC exposures were associated with grade \u22652 PN and grade \u22653 neutropenia occurrence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>BV pharmacokinetics in adult and paediatric patients were consistent. BV ADC exposures were lower in patients aged 2 to &lt;12 years <jats:italic>vs<\/jats:italic>. \u226512 years, but no apparent clinically relevant differences in efficacy, grade \u22652 PN or grade \u22653 neutropenia were observed. These data support body weight\u2010based dosing of BV in patients irrespective of age; thus, dose adjustment in those 2 to &lt;12 years does not appear warranted.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16128","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:24:41Z","timestamp":1718238281000},"page":"2299-2313","source":"Crossref","is-referenced-by-count":6,"title":["Time\u2010varying brentuximab vedotin pharmacokinetics and weight\u2010based dosing in paediatric patients despite lower exposure in those aged 2 to &lt;6 and 6\u201311\u2009years"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1646-094X","authenticated-orcid":false,"given":"Daping","family":"Zhang","sequence":"first","affiliation":[{"name":"Translational Clinical Sciences, Research and Development Pfizer  Bothell Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zufei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Translational Sciences, Oncology Research and Development Pfizer  Bothell Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Translational Sciences, Oncology Research and Development Pfizer  Bothell Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keenan","family":"Fenton","sequence":"additional","affiliation":[{"name":"Oncology Statistics, Oncology Research and Development Pfizer  Bothell Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta","family":"Jain","sequence":"additional","affiliation":[{"name":"Oncology Research and Development Pfizer  Bothell Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Garg","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Translational Sciences, Oncology Research and Development Pfizer  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen Lin","family":"Chia","sequence":"additional","affiliation":[{"name":"Translational Clinical Sciences, Research and Development Pfizer  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Seagen Inc.ADCETRIS [prescribing information].Seagen Inc.;2023."},{"key":"e_1_2_10_3_1","unstructured":"US Food and Drug Administration.FDA approves brentuximab vedotin in combination with chemotherapy for pediatric patients with classical Hodgkin lymphoma. 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