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At present, this drug is being prescribed mainly based on the clinical experience of doctors. The potential effects of clinical and demographic variables on the bioavailability and therapeutic effectiveness of febuxostat are not being considered. In this study a physiologically based pharmacokinetic (PBPK) model of febuxostat was developed, thereby providing a theoretical basis for the individualized dosing of this drug in gout patients. The plasma concentration\u2013time profiles corresponding to healthy subjects and gout patients with normal kidney function were simulated and validated; then, the model was used to predict the pharmacokinetic (PK) data of the drug in gout patients suffering from varying degrees of impaired kidney function. The error values (the predicted value\/observed value) were used to validate the simulated PK parameters predicted by the PBPK model, including the area under the plasma concentration\u2013time curve, the maximum plasma concentration, and time to maximum plasma concentration. Considering that to all error fold changes were smaller than 2, the PBPK model was. In subjects suffering from mild kidney impairment, moderate kidney impairment, severe kidney impairment, and endstage kidney disease (ESRD), the predicted AUC<jats:sub>0\u201024h<\/jats:sub> values increased by 1.62, 1.74, 2.27, and 2.65\u2010fold, respectively, compared to gout patients with normal kidney function. Overall, the results showed that the PBPK model constructed in this study predict the pharmacokinetic changes in gout patients suffering from varying degrees of impaired kidney function.<\/jats:p>","DOI":"10.1002\/bdd.2325","type":"journal-article","created":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T07:39:22Z","timestamp":1656056362000},"page":"140-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Simulation of febuxostat pharmacokinetics in healthy subjects and patients with impaired kidney function using physiologically based pharmacokinetic modeling"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0476-9787","authenticated-orcid":false,"given":"Yichao","family":"Xu","sequence":"first","affiliation":[{"name":"Center of Clinical Pharmacology The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinliang","family":"Chen","sequence":"additional","affiliation":[{"name":"Center of Clinical Pharmacology The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zourong","family":"Ruan","sequence":"additional","affiliation":[{"name":"Center of Clinical Pharmacology The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Center of Clinical Pharmacology The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Yang","sequence":"additional","affiliation":[{"name":"Center of Clinical Pharmacology The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Hu","sequence":"additional","affiliation":[{"name":"Center of Clinical Pharmacology The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honggang","family":"Lou","sequence":"additional","affiliation":[{"name":"Center of Clinical Pharmacology The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000573"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050373"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1613"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.1767"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00488"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1076029616687849"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2018.09.009"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24180"},{"issue":"4","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1097\/RHU.0b013e31821d36f2","article-title":"A repeated oral administration study of febuxostat (TMX\u201067), a non\u2010purine\u2010selective inhibitor of xanthine oxidase, in patients with impaired renal function in Japan: Pharmacokinetic and pharmacodynamic study","volume":"17","author":"Hosoya T.","year":"2011","journal-title":"Journal of Clinical Rheumatology"},{"issue":"1","key":"e_1_2_9_11_1","first-page":"16","article-title":"Progress in methodology of establishing physiologically based pharmacokinetic models","volume":"49","author":"Jin Y. 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