{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:24:47Z","timestamp":1760059487889,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hunan Science and Technology Youth Talent Support Program","award":["2023TJ-N20","2023RC3232","2023JJ50406"],"award-info":[{"award-number":["2023TJ-N20","2023RC3232","2023JJ50406"]}]},{"name":"science and technology innovation Program of Hunan Province","award":["2023TJ-N20","2023RC3232","2023JJ50406"],"award-info":[{"award-number":["2023TJ-N20","2023RC3232","2023JJ50406"]}]},{"name":"Hunan Provincial Natural Science Foundation","award":["2023TJ-N20","2023RC3232","2023JJ50406"],"award-info":[{"award-number":["2023TJ-N20","2023RC3232","2023JJ50406"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Avatrombopag (AVA), a thrombopoietin receptor agonist used to treat thrombocytopenia in patients with chronic liver disease, exhibits significant pharmacokinetic (PK) variability, particularly under fasting conditions. This study investigates the combined influence of food intake and genetic polymorphisms in CYP2C9 and ABCB1 on the PK and pharmacodynamics (PD) of AVA, with the goal of informing individualized dosing strategies. Methods: A pharmacogenetic analysis was conducted in 92 healthy participants, who received 20 mg of AVA under both fasting and fed conditions. A population PK\/PD model was developed to evaluate the covariates effects on the PK variability. Monte Carlo simulations were used to predict AVA exposure and platelet count profiles under diverse dosing scenarios. Results: Food intake significantly reduced PK variability, with approximately 50% reductions in clearance (CL\/F) and volume of distribution (Vd\/F) compared to fasting conditions. Under fed conditions, CYP2C9 intermediate metabolizers showed a 1.70-fold increase in exposure compared to normal metabolizers, but this difference was not observed under fasting conditions. ABCB1 polymorphisms showed minimal impact, with the exception of ABCB1 (C1236T) heterozygotes, which exhibited 1.37-fold increased exposure. Despite the observed PK variability, simulations demonstrated a consistent platelet count response across dosing regimens. Conclusions: While food intake and genetic polymorphisms in CYP2C9 and ABCB1 influenced AVA PK, these factors may not require dose adjustments, as platelet count responses remained consistent across genotypes and dosing conditions in the Chinese participants. These findings support simplified dosing strategies without the need for pharmacogenetic testing in Chinese individuals and may contribute to more individualized thrombocytopenia management.<\/jats:p>","DOI":"10.3390\/ph18060903","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T03:37:07Z","timestamp":1750131427000},"page":"903","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of the ABCB1 Gene Polymorphism and Food Effects on the Avatrombopag Pharmacokinetics in Chinese Individuals: A Population Pharmacokinetic\/Pharmacodynamic Analysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5595-3195","authenticated-orcid":false,"given":"Xin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 200437, China"},{"name":"Changsha Phamark Data Co., Ltd., Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulu","family":"Chen","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha 410013, China"},{"name":"Department of Pharmacy, The Affiliated Hospital, Xiangnan University, Chenzhou 423043, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gehang","family":"Ju","sequence":"additional","affiliation":[{"name":"Changsha Phamark Data Co., Ltd., Changsha 410013, China"},{"name":"Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Li","sequence":"additional","affiliation":[{"name":"Changsha Phamark Data Co., Ltd., Changsha 410013, China"},{"name":"Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha 410013, China"},{"name":"Changsha Duxact Clinical Laboratory Co., Ltd., Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bijue","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 200437, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunzhou","family":"Fei","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha 410013, China"},{"name":"Changsha Duxact Clinical Laboratory Co., Ltd., Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xintong","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha 410013, China"},{"name":"Changsha Duxact Clinical Laboratory Co., Ltd., Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Gao","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5795-1550","authenticated-orcid":false,"given":"Qingfeng","family":"He","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 200437, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3295-619X","authenticated-orcid":false,"given":"Xiao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 200437, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9987-0203","authenticated-orcid":false,"given":"Dongsheng","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Changsha Phamark Data Co., Ltd., Changsha 410013, China"},{"name":"Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha 410013, China"},{"name":"Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410017, China"},{"name":"Changsha Duxact Clinical Laboratory Co., Ltd., Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/cpdd.349","article-title":"Pharmacokinetics, Pharmacodynamics, Pharmacogenomics, Safety, and Tolerability of Avatrombopag in Healthy Japanese and White 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