{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T03:11:04Z","timestamp":1768014664670,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:p>Coronavirus disease 2019 (COVID\u201019)\u2010associated pulmonary aspergillosis superinfection with cytokine storm is associated with increased mortality. This study aimed to establish a physiologically\u2010based pharmacokinetic (PK) model to investigate the disease\u2010drug\u2013drug interactions between voriconazole and nirmatrelvir\/ritonavir in patients with COVID\u201019 with elevated interleukin\u20106 (IL\u20106) levels carrying various CYP2C19 phenotypes. The model was constructed and validated using PK data on voriconazole, ritonavir, and IL\u20106, and was subsequently verified against clinical data from 78 patients with COVID\u201019. As a result, the model predicted voriconazole, ritonavir, and IL\u20106 PK parameters and drug\u2013drug interaction\u2010related fold changes in healthy subjects and patients with COVID\u201019 with acceptable prediction error, demonstrating its predictive capability. Simulations indicated ritonavir could increase voriconazole exposure to CYP2C19 intermediate and poor metabolizers rather than decrease it, in contrast to what is indicated in the drug package insert. However, the predicted ritonavir exposures were comparable across subjects. In patients with COVID\u201019, both ritonavir and IL\u20106 increased voriconazole trough concentrations, which may lead to CYP2C19 phenotype\u2010dependent overexposure. In conclusion, COVID\u201019\u2010induced IL\u20106 elevation and ritonavir increased voriconazole exposure, and the magnitude of interactions was influenced by CYP2C19 phenotype. Thus, caution is warranted when prescribing voriconazole concomitantly with Paxlovid in patients with COVID\u201019.<\/jats:p>","DOI":"10.1002\/cpt.3222","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T06:11:30Z","timestamp":1709359890000},"page":"363-371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Physiologically Based Pharmacokinetic Modeling to Investigate the Disease\u2010Drug\u2013Drug Interactions between Voriconazole and Nirmatrelvir\/Ritonavir in <scp>COVID<\/scp>\u201019 Patients with <scp>CYP2C19<\/scp> Phenotypes"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3264-4092","authenticated-orcid":false,"given":"Peile","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy the First Affiliated Hospital of Zhengzhou University  Zhengzhou China"},{"name":"Henan Key Laboratory of Precision Clinical Pharmacy Zhengzhou University  Zhengzhou China"},{"name":"Henan Engineering Research Center for Application &amp; Translation of Precision Clinical Pharmacy Zhengzhou University  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7962-0330","authenticated-orcid":false,"given":"Shuaibing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy the First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2113-6578","authenticated-orcid":false,"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy the First Affiliated Hospital of Zhengzhou University  Zhengzhou China"},{"name":"Henan Key Laboratory of Precision Clinical Pharmacy Zhengzhou University  Zhengzhou China"},{"name":"Henan Engineering Research Center for Application &amp; Translation of Precision Clinical Pharmacy Zhengzhou University  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30847-1"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(22)00259-4"},{"key":"e_1_2_9_3_1","unstructured":"World Health Organization.Therapeutics and COVID\u201019<https:\/\/www.who.int\/publications\/i\/item\/WHO\u20102019\u2010nCoV\u2010therapeutics\u20102023.1>."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2016.11.025"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.583"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2703"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.7326\/M22-0281"},{"key":"e_1_2_9_8_1","volume-title":"VFEND\u2122 (voriconazole). US prescribing information","author":"Pfizer Inc","year":"2022"},{"key":"e_1_2_9_9_1","volume-title":"PAXLOVID\u2122 (nirmatrelvir tablets; ritonavir tablets). US prescribing information","author":"Pfizer Inc","year":"2023"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad159"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.farma.2022.12.018"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2006.04.004"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.798"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.891456"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13627"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00856-z"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2015.58"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2687"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2122"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1721"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01067-1"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-019-0309-y"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2141"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2402"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12946"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-016-9890-5"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00207-21"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000561"},{"key":"e_1_2_9_29_1","first-page":"2459","article-title":"Bacterial and fungal coinfection in individuals with coronavirus: a rapid review to support COVID\u201019 antimicrobial prescribing","volume":"71","author":"Rawson T.M.","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-016-0416-1"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-022-03289-9"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00526-07"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1998.tb04398.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-020-00668-8"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.791922"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.122.000926"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-022-01173-8"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12040764"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.3222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,28]],"date-time":"2024-09-28T08:12:53Z","timestamp":1727511173000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.3222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/cpt.3222"],"URL":"https:\/\/doi.org\/10.1002\/cpt.3222","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"2023-11-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}