{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:20:31Z","timestamp":1780320031329,"version":"3.54.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Natural Science Funding of Zhejiang Province","award":["LGF20H310001"],"award-info":[{"award-number":["LGF20H310001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973397"],"award-info":[{"award-number":["81973397"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wenzhou Science and Technology Bureau Project","award":["Y20180130"],"award-info":[{"award-number":["Y20180130"]}]},{"name":"Project of Zhejiang Pharmaceutical Association","award":["2018ZYY59"],"award-info":[{"award-number":["2018ZYY59"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>In this study, we aimed to investigate the potential interaction of apatinib and buspirone and underlying mechanism.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>UPLC-MS\/MS assay was applied to determine the concentrations of buspirone and its main metabolites (1-PP and 6-OH buspirone) after incubated with liver microsomes. Moreover, the connection of in vitro and in vivo was further determined. Sprague Dawley rats were randomly divided into two groups: group A (20 mg\/kg buspirone) and group B (buspirone vs 40 mg\/kg apatinib). Tail vein blood was collected and subjected to the UPLC-MS\/MS detection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Apatinib inhibited the generations of 1-PP and 6-OH buspirone dose-dependently with IC50 of 1.76 and 2.23 \u03bcm in RLMs, and 1.51 and 1.48 \u03bcm in HLMs, respectively. There was a mixed mechanism underlying such an inhibition effect. In rat, AUC(0\u2013t), AUC(0\u2013\u221e), Tmax and Cmax of buspirone and 6-OH buspirone increased significantly while co-administering with apatinib, but Vz\/F and CLz\/F decreased obviously while comparing group A with group B .<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Apatinib suppresses the CYP450 based metabolism of buspirone in a mixed mechanism and boosted the blood exposure of prototype drug and 6-OH buspirone dramatically. Therefore, extra caution should be taken when combining apatinib with buspirone in clinic.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jphp.13320","type":"journal-article","created":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T05:57:59Z","timestamp":1593583079000},"page":"1405-1411","source":"Crossref","is-referenced-by-count":7,"title":["The effect of apatinib on pharmacokinetic profile of buspirone both <i>in vivo<\/i> and <i>in vitro<\/i>"],"prefix":"10.1093","volume":"72","author":[{"given":"Xiao-dan","family":"Zhang","sequence":"first","affiliation":[{"name":"The Seventh People\u2019s Hospital of Wenzhou , Wenzhou, Zhejiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-hui","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou, Zhejiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dao-xing","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou, Zhejiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-wei","family":"You","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou, Zhejiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-xia","family":"Hu","sequence":"additional","affiliation":[{"name":"Jinhua Hospital of Zhejiang University and Jinhua Municipal Central Hospital , Jinhua, Zhejiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing-bing","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou, Zhejiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5169-4696","authenticated-orcid":false,"given":"Guo-xin","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou, Zhejiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9985-3852","authenticated-orcid":false,"given":"Jian-chang","family":"Qian","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou, Zhejiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,1]]},"reference":[{"key":"2024103012341313000_jphp13320-cit-0001","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1002\/pon.4761","article-title":"Latent class analysis differentiation of adjustment disorder and demoralization, more severe depressive and anxiety disorders, and somatic symptoms in patients with cancer","volume":"11","author":"Bobevski","year":"2018","journal-title":"Psychooncology"},{"key":"2024103012341313000_jphp13320-cit-0002","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.4155\/bio-2019-0214","article-title":"Determination of apatinib and its three active metabolites by UPLC-MS\/MS in a Phase IV clinical trial in NSCLC patients","volume":"22","author":"Guan","year":"2019","journal-title":"Bioanalysis"},{"key":"2024103012341313000_jphp13320-cit-0003","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1080\/14740338.2018.1535592","article-title":"The safety of apatinib for the treatment of gastric cancer","volume":"11","author":"Geng","year":"2018","journal-title":"Expert Opin Drug Saf"},{"key":"2024103012341313000_jphp13320-cit-0004","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1186\/1471-2407-14-820","article-title":"Multicenter phase II study of apatinib in non-triple-negative metastatic breast cancer","volume":"14","author":"Hu","year":"2014","journal-title":"BMC Cancer"},{"issue":"5 Pt A","key":"2024103012341313000_jphp13320-cit-0005","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1016\/j.bbadis.2018.02.014","article-title":"Novel role of apatinib as a multi-target RTK inhibitor in the direct suppression of hepatocellular carcinoma cells","volume":"1864","author":"Li","year":"2018","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"2024103012341313000_jphp13320-cit-0006","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1080\/03639045.2019.1569042","article-title":"Effects of ketoconazole, voriconazole, and itraconazole on the pharmacokinetics of apatinib in rats","volume":"4","author":"Lou","year":"2019","journal-title":"Drug Dev Indust Pharm"},{"key":"2024103012341313000_jphp13320-cit-0007","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1124\/dmd.118.084905","article-title":"Mechanisms and clinical significance of pharmacokinetic-based drug-drug interactions with drugs approved by the U.S. food and drug administration in 2017","volume":"2","author":"Yu","year":"2019","journal-title":"Drug Metab Dispos"},{"key":"2024103012341313000_jphp13320-cit-0008","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1124\/dmd.112.050310","article-title":"Metabolism and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor apatinib in humans","volume":"6","author":"Ding","year":"2013","journal-title":"Drug Metab Dispos"},{"key":"2024103012341313000_jphp13320-cit-0009","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxlet.2018.08.010","article-title":"Evaluation of the inhibition effects of apatinib on human and rat cytochrome P450","volume":"297","author":"Bao","year":"2018","journal-title":"Toxicol Lett"},{"key":"2024103012341313000_jphp13320-cit-0010","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1097\/00004714-199902000-00014","article-title":"Buspirone: future directions","volume":"1","author":"Apter","year":"1999","journal-title":"J Clin Psychopharmacol"},{"key":"2024103012341313000_jphp13320-cit-0011","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0002-9343(86)90325-6","article-title":"Buspirone: review of its pharmacology and current perspectives on its mechanism of action","volume":"3b","author":"Eison","year":"1986","journal-title":"Am J Med"},{"issue":"Pt 2","key":"2024103012341313000_jphp13320-cit-0012","first-page":"4","article-title":"Buspirone: chemical profile of a new class of anxioselective agents","volume":"12","author":"Temple","year":"1982","journal-title":"J Clin Psychiat"},{"key":"2024103012341313000_jphp13320-cit-0013","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1600-0773.1991.tb01289.x","article-title":"Molecular basis of buspirone's anxiolytic action","volume":"3","author":"Tunnicliff","year":"1991","journal-title":"Pharmacol Toxicol"},{"key":"2024103012341313000_jphp13320-cit-0014","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1124\/dmd.107.015768","article-title":"6-Hydroxybuspirone is a major active metabolite of buspirone: assessment of pharmacokinetics and 5-hydroxytryptamine1A receptor occupancy in rats","volume":"8","author":"Wong","year":"2007","journal-title":"Drug Metab Dispos"},{"key":"2024103012341313000_jphp13320-cit-0015","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.2165\/00003495-200262110-00005","article-title":"Generalised anxiety disorder: treatment options","volume":"11","author":"Sramek","year":"2002","journal-title":"Drugs"},{"key":"2024103012341313000_jphp13320-cit-0016","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1124\/dmd.104.000836","article-title":"Cytochrome P450 3A-mediated metabolism of buspirone in human liver microsomes","volume":"4","author":"Zhu","year":"2005","journal-title":"Drug Metab Dispos"},{"key":"2024103012341313000_jphp13320-cit-0017","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0006-3223(02)01643-8","article-title":"Is there a role for 5-HT1A agonists in the treatment of depression?","volume":"3","author":"Blier","year":"2003","journal-title":"Biol Psychiat"},{"key":"2024103012341313000_jphp13320-cit-0018","doi-asserted-by":"crossref","first-page":"114","DOI":"10.2165\/00003495-198632020-00002","article-title":"A preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic","volume":"2","author":"Goa","year":"1986","journal-title":"Drugs"},{"key":"2024103012341313000_jphp13320-cit-0019","article-title":"Behavioral effects of buspirone in a mouse model of posttraumatic stress disorder","volume":"112380","author":"Malikowska-Racia","year":"2019","journal-title":"Behav Brain Res"},{"key":"2024103012341313000_jphp13320-cit-0020","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.jpba.2011.03.043","article-title":"Buspirone, fexofenadine, and omeprazole: quantification of probe drugs and their metabolites in human plasma","volume":"5","author":"Gor","year":"2011","journal-title":"J Pharm Biomed Anal"},{"key":"2024103012341313000_jphp13320-cit-0021","first-page":"634","article-title":"Metabolism of the antianxiety drug buspirone in human subjects","volume":"6","author":"Jajoo","year":"1989","journal-title":"Drug Metab Dispos"},{"key":"2024103012341313000_jphp13320-cit-0022","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1177\/0091270006292250","article-title":"Pharmacokinetics of a newly identified active metabolite of buspirone after administration of buspirone over its therapeutic dose range","volume":"11","author":"Dockens","year":"2006","journal-title":"J Clin Pharmacol"},{"key":"2024103012341313000_jphp13320-cit-0023","doi-asserted-by":"crossref","first-page":"277","DOI":"10.2165\/00003088-199936040-00003","article-title":"Clinical pharmacokinetics and pharmacodynamics of buspirone, an anxiolytic drug","volume":"4","author":"Mahmood","year":"1999","journal-title":"Clin Pharmacokinet"},{"key":"2024103012341313000_jphp13320-cit-0024","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/03602530902843483","article-title":"Polymorphism of human cytochrome P450 enzymes and its clinical impact","volume":"2","author":"Zhou","year":"2009","journal-title":"Drug Metab Rev"},{"key":"2024103012341313000_jphp13320-cit-0025","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.fct.2012.10.008","article-title":"The exposure of highly toxic aconitine does not significantly impact the activity and expression of cytochrome P450 3A in rats determined by a novel ultra performance liquid chromatography-tandem mass spectrometric method of a specific probe buspirone","volume":"51","author":"Zhu","year":"2013","journal-title":"Food Chem Toxicol"},{"key":"2024103012341313000_jphp13320-cit-0026","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1002\/ptr.5365","article-title":"Modulation of cytochrome P450 activity by 18beta-glycyrrhetic acid and its consequence on buspirone pharmacokinetics in rats","volume":"8","author":"Kim","year":"2015","journal-title":"Phytother Res"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjphp.13320","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jphp.13320","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jphp.13320","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/72\/10\/1405\/60225281\/jphp13320.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/72\/10\/1405\/60225281\/jphp13320.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T17:50:57Z","timestamp":1730310657000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/72\/10\/1405\/6132703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,1]]},"references-count":26,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10,1]]},"published-print":{"date-parts":[[2020,10,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jphp.13320","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,10]]},"published":{"date-parts":[[2020,10,1]]}}}