{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:38:05Z","timestamp":1789558685270,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. This analysis assessed the suitability of a fixed\u2010dose regimen of tezepelumab 210 mg every 4 weeks (Q4W) in adults and adolescents with severe, uncontrolled asthma. A population pharmacokinetic model was developed using data from 1368 patients with asthma or healthy participants enrolled in 8 clinical studies (phases 1\u20103). Tezepelumab exposure\u2010efficacy relationships were analyzed in the phase 3 NAVIGATOR study (NCT03347279), using asthma exacerbation rates over 52 weeks and changes in pre\u2010bronchodilator forced expiratory volume in 1 s at week 52. Tezepelumab pharmacokinetics were well characterized by a 2\u2010compartment linear disposition model with first\u2010order absorption and elimination following subcutaneous and intravenous administration at 2.1\u2010420 and 210\u2010700 mg, respectively. There were no clinically relevant effects on tezepelumab pharmacokinetics from age (\u226512 years), sex, race\/ethnicity, renal or hepatic function, disease severity (inhaled corticosteroid dose level), concomitant asthma medication use, smoking history, or anti\u2010drug antibodies. Body weight was the most influential covariate on tezepelumab exposure, but no meaningful differences in efficacy or safety were observed across body weight quartiles in patients with asthma who received tezepelumab 210 mg subcutaneously Q4W. There was no apparent relationship between tezepelumab exposure and efficacy at this dose regimen, suggesting that it is on the plateau of the exposure\u2010response curve of tezepelumab. In conclusion, a fixed\u2010dose regimen of tezepelumab 210 mg subcutaneously Q4W is appropriate for eligible adults and adolescents with severe, uncontrolled asthma.<\/jats:p>","DOI":"10.1002\/jcph.2433","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T04:59:47Z","timestamp":1713416387000},"page":"908-921","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Population Pharmacokinetic Modeling and Exposure\u2013Efficacy and Body Weight\u2013Response Analyses for Tezepelumab in Patients With Severe, Uncontrolled Asthma"],"prefix":"10.1002","volume":"64","author":[{"given":"Yanan","family":"Zheng","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology, AstraZeneca  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubna","family":"Abuqayyas","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modeling and Simulation, Amgen  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Quartino","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology, AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Guan","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology, AstraZeneca  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Gao","sequence":"additional","affiliation":[{"name":"Shanghai Qiangshi Information Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Qiangshi Information Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c5sa","family":"Hellqvist","sequence":"additional","affiliation":[{"name":"Biometrics, Late\u2010stage Development Respiratory and Immunology, AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene","family":"Colice","sequence":"additional","affiliation":[{"name":"Late\u2010Stage Development Respiratory and Immunology, AstraZeneca  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology  AstraZeneca Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13378"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/JAA.S327659"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9082397"},{"key":"e_1_2_11_5_1","unstructured":"Global Initiative for Asthma.Global strategy for asthma management and prevention.2022. 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