{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T15:05:44Z","timestamp":1783177544789,"version":"3.54.6"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFC2008303"],"award-info":[{"award-number":["2020YFC2008303"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFC2008306"],"award-info":[{"award-number":["2020YFC2008306"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Apatinib is widely used in Chinese cancer patients. As the in vivo drug disposition of apatinib has large individual differences, adverse events are prone to occur. Cytochrome P450 (CYP)3A5 and cancer types maybe the main factors affecting this individual differences. The objective of our study was to establish a population pharmacokinetics (PK) model of apatinib in adult cancer patients, and to explore optimal dosage regimens for individualized treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult patients with various types of cancer treated with apatinib were enrolled. The concentration of apatinib in plasma was determined by high\u2010performance liquid chromatography\u2013tandem mass spectrometry. CYP3A5 genotype was determined using TaqMan allelic discrimination technique. The population PK model was developed by NONMEM V7.4. The dosing regimen was optimized based on Monte Carlo simulations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A population PK model of apatinib in adult cancer patient was established. CYP3A5 genotype and systemic cancer type (digestive system cancers, nondigestive system cancers) were the most significant covariates for PK parameters. Patients with CYP3A5*1 expressers (CYP3A5*1\/*1 and CYP3A5*1\/*3) had lower apparent clearance and apparent volume of distribution than patients who do not express CYP3A5*1 (CYP3A5*3\/*3). Patients with nondigestive system cancer had higher apparent volume of distribution and absorption rate constant than digestive system cancer. The results of dose simulation suggest that the apatinib dose in patients who do not express CYP3A5*1 should be 33.33\u201350.00% higher than that in CYP3A5*1 expressers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A population PK model of apatinib in adult cancer patients was established. CYP3A5 genotype and systemic cancer type had concurrent effects on PK parameters. CYP3A5 patients who do not express CYP3A5*1 required higher doses.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15665","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T16:54:16Z","timestamp":1674233656000},"page":"1862-1872","source":"Crossref","is-referenced-by-count":8,"title":["Population pharmacokinetics and pharmacogenetics of apatinib in adult cancer patients"],"prefix":"10.1111","volume":"89","author":[{"given":"Xin\u2010Mei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan\u2010Pan","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi\u2010Xuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy China \u2010 Japan Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Kan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin\u2010Lin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke\u2010Guang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Yi","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye\u2010Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University &amp; 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