{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:58:55Z","timestamp":1790315935920,"version":"4.1.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Chemother Pharmacol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aimed to characterize the pharmacokinetics (PK) of pirtobrutinib, a highly selective and noncovalent Bruton\u2019s tyrosine kinase (BTK) inhibitor, in adult patients with hematological malignancies using data from the Phase 1\/2 BRUIN study (NCT03740529).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Pirtobrutinib was administered as monotherapy at doses ranging from 25 to 300\u00a0mg once daily (QD). PK samples were collected at multiple time points, including intensive sampling on Cycle (C) 1 Day (D) 1, C1D8, C2D1, and C4D1 for Phase 1 dose-escalation, and sparse sampling on C1D8 and C4D1 for Phase 1 dose-expansion and Phase 2. Population PK (popPK) analysis used nonlinear mixed-effects modeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 4487 evaluable pirtobrutinib concentrations obtained from 595 patients were included in the popPK analysis. Pirtobrutinib PK was well characterized by a 2-compartment model with linear clearance and 4-transit compartments for absorption. The mean elimination half-life was estimated to be 18.8\u00a0h. At the recommended Phase 2 dose (200\u00a0mg QD), the steady-state mean maximum drug concentration was 6460ng\/mL, the mean minimum was 2260ng\/mL, and the mean area under the concentration-time curve was 91300ng*h\/mL. Pirtobrutinib disposition was significantly affected by body weight, renal function, and serum albumin, but not by formulation, cancer type, age, sex, race, ethnicity, or mild hepatic impairment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>With the proposed starting dose of 200\u00a0mg QD, most patients (96%) were expected to exceed 90% BTK inhibition, across the entire dosing interval, indicating extensive and durable engagement of the drug target. No dose adjustments based on body weight, serum albumin or renal function were recommended.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>NCT03740529.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00280-026-04951-4","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:25:26Z","timestamp":1790267126000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetic analysis of pirtobrutinib, a non-covalent BTK inhibitor, in patients with hematological malignancies from the Phase 1\/2 BRUIN study"],"prefix":"10.1007","volume":"96","author":[{"given":"Robert","family":"Bell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunice","family":"Yuen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonya C.","family":"Chapman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"4951_CR1","unstructured":"Mukkamalla SKR, Taneja A, Malipeddi D, Master SR (2023) Chronic lymphocytic leukemia. 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FDA grants accelerated approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma (2023) Available at: FDA grants traditional approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma | FDA. Accessed 21 Jul 2026","DOI":"10.1080\/14796694.2025.2567834"},{"key":"4951_CR7","doi-asserted-by":"publisher","unstructured":"Jurczak W, Kwiatek M, Czyz J, Roberto de Mattos E, Eom KS, Egle A, Panovska A, Popova ZG, Shih HJ, Casado Montero LF, Sportoletti P, Hua VM, D\u2019Olimpio JT, Iida S, Ito R, Bao K, Fink A, Su W, Ruppert AS, Levy A, Wrobel T (2026) BRUIN CLL-313: Randomized Phase III Trial of Pirtobrutinib Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma. 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