{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:57:09Z","timestamp":1792065429649,"version":"4.4.0"},"reference-count":72,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:00:00Z","timestamp":1716336000000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Venetoclax, a highly potent BCL\u20102 inhibitor, is indicated for treatment of some hematologic malignancies as monotherapy, and\/or in combination with other agents. Venetoclax pharmacokinetics has been extensively characterized in patients and healthy participants. After oral dosing, the median time to reach maximum plasma concentration ranged from 5 to 8\u2009h and harmonic mean half\u2010life ranged from 14 to 18\u2009h. Food increases venetoclax bioavailability by 3\u20135\u2010fold and venetoclax should be administered with food to ensure adequate and consistent bioavailability. Venetoclax is eliminated via cytochrome P450 (CYP)3A metabolism, and a negligible amount of unchanged drug is excreted in urine. Strong CYP3A\/P\u2010glycoprotein inhibitors increased venetoclax exposures (AUC) by 1.44\u2010 to 6.90\u2010fold while a significant decrease (71%) has been observed when dosed with strong CYP3 inducers. Venetoclax does not inhibit or induce CYP enzymes or transporters. Venetoclax pharmacokinetics is not appreciably altered by age, weight, sex, but the exposure is up to twofold higher in participants from Asian countries. Mild\u2010to\u2010severe renal impairment or end\u2010stage renal disease do not alter venetoclax exposures, and venetoclax is not cleared by dialysis. Although mild\u2010to\u2010moderate hepatic impairment does not affect venetoclax exposures, twofold higher exposure was observed in subjects with severe hepatic impairment. Venetoclax exposure is comparable across patients with different hematologic malignancies and healthy participants. Overall, venetoclax exposure is only affected by food and CYP3A modulators and is only higher in Asian subjects and subjects with severe hepatic impairment. Venetoclax exposure\u2013response relationships are malignancy\u2010dependent and can be different between monotherapy and combination therapy.<\/jats:p>","DOI":"10.1111\/cts.13807","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T06:50:34Z","timestamp":1716447034000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Clinical pharmacokinetics and pharmacodynamics of venetoclax, a selective B\u2010cell lymphoma\u20102 inhibitor"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9261-1583","authenticated-orcid":false,"given":"Ahmed Hamed","family":"Salem","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy Ain Shams University  Cairo Egypt"},{"name":"AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2945-0449","authenticated-orcid":false,"given":"Rajeev M.","family":"Menon","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210220"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.34.7898"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70261-8"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm800669s"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5836"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404719"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-12-400929"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.01.037"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3048"},{"key":"e_1_2_12_11_1","unstructured":"Venclexta (venetoclax) [US prescribing information].2023.AbbVie Inc."},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1713976"},{"key":"e_1_2_12_13_1","unstructured":"AbbVie.Press release: AbbVie Receives European Commission Approval of VENCLYXTO\u00ae Combination Regimen for Patients with Previously\u2010Untreated Chronic Lymphocytic Leukemia.https:\/\/news.abbvie.com\/news\/press\u2010releases\/abbvie\u2010receives\u2010european\u2010commission\u2010approval\u2010venclyxto\u2010combination\u2010regimen\u2010for\u2010patients\u2010with\u2010previously\u2010untreated\u2010chronic\u2010lymphocytic\u2010leukemia.htm. Accessed March 12 2020."},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.055053"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-022-01172-4"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.116.071613"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13144"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.81795"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1513257"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.821"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13175"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2017.01.003"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.730"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-018-0793-y"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-016-0485-9"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.741"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy256"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.4320"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-0313"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-788786"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-016-9927-9"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2248"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(92)90010-G"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0009-9236(03)00187-5"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-1465"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30060-7"},{"key":"e_1_2_12_37_1","doi-asserted-by":"crossref","unstructured":"BadawiM GopalakrishnanS EngelhardtB et\u00a0al.Proposed scheme for dosing venetoclax in pediatric patients with relapsed\/refractory acute myeloid leukemia: analysis of developmental pharmacokinetics and exposure\u2010response relationships. American Society of Hematology Annual Meeting (ASH). San Diego California.2020.","DOI":"10.1182\/blood-2020-139593"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.395"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-020-03024-3"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2964"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00746-4"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15935"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0000000000000522"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12739"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2016.10.212"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-021-01919-z"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-21-0077"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-017-2403-3"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.858"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-020-04179-w"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2140"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2017.1381779"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-788323"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(17)30012-8"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30010-X"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1815281"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.01600"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.00807"},{"key":"e_1_2_12_59_1","doi-asserted-by":"crossref","unstructured":"AlaeiS WangY LiuY SchieleJ DengR ShillerD MarroumP MenonR SalemAH. Venetoclax clinical pharmacokinetics after administration of crushed ground or whole tablets.Clin Ther.2024. doi:10.1016\/clinthera.2024.03.012","DOI":"10.1016\/j.clinthera.2024.03.012"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2373"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2005"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-016-3144-1"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12665"},{"issue":"1","key":"e_1_2_12_64_1","first-page":"S67","article-title":"Modeling M\u2010protein dynamics in subjects with relapsed\/refractory multiple myeloma receiving venetoclax: utility of early M\u2010protein monitoring to predict progression free survival","volume":"115","author":"Liu S","year":"2024","journal-title":"Clin Pharmacol Ther"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2019.1657575"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-022-02170-w"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2646"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2017.1361024"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.712"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.3222"},{"key":"e_1_2_12_71_1","doi-asserted-by":"crossref","unstructured":"BadawiM EngelhardtB DobkowskaE et\u00a0al.Exposure\u2010response analysis of venetoclax in combination with carfilzomib and dexamethason in t(11;14)\u2010positive relapsed\/refractory multiple myeloma patients. Athens Greece: The 20th International Myeloma Society Annual Meeting.2023.","DOI":"10.1016\/S2152-2650(23)01847-5"},{"key":"e_1_2_12_72_1","doi-asserted-by":"crossref","unstructured":"BadawiM EngelhardtB BadilloJ et\u00a0al.Exposure\u2010response analysis supports a lower dose of venetoclax in t(11;14)\u2010positive relapsed\/refractory multiple myeloma patients when combined with daratumumab and dexamethasone. New Orleans Louisiana: American Society of Hematology Annual Meeting (ASH).2022.","DOI":"10.1182\/blood-2022-166429"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-016-0453-9"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13807","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T11:26:54Z","timestamp":1716895614000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":72,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/cts.13807"],"URL":"https:\/\/doi.org\/10.1111\/cts.13807","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"2023-12-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13807"}}