{
    "abstract": "Digoxin is a commonly used cardiac glycoside drug in clinical practice, primarily transported by P-glycoprotein (P-gp) and susceptible to the influence of P-gp inhibitors/inducers. Concurrent administration of ritonavir and digoxin may significantly increase the plasma concentration of digoxin. Due to the narrow therapeutic window of digoxin, combined use may lead to severe toxic effects.\nUtilize a Physiology-Based Pharmacokinetic (PBPK) model to simulate and predict the impact of the interaction between ritonavir and digoxin on the pharmacokinetics (PK) of digoxin, and provide recommendations for the combined medication regimen.\nUsing PK-Sim\nAccording to the model simulations, the steady-state exposure of digoxin increased by 86.5% and 90.2% for oral administration, and 80.2% and 90.2% for intravenous administration, respectively, when 0.25\u00a0mg or 0.5\u00a0mg of digoxin was administered concurrently with ritonavir. By reducing the dose of digoxin by 45% or doubling the oral administration interval, similar steady-state concentrations can be achieved compared to when the drugs are not co-administered.\nIn clinical practice, the influence of drug interactions on the plasma concentration changes of digoxin within the body should be considered to ensure the safety and effectiveness of treatment.",
    "authors": [
        {
            "affiliation": "Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China.\nWannan Medical College, No. 22, Wenchang West Road, Yijiang District, Wuhu, 241002, China.",
            "firstname": "Youjun",
            "initials": "Y",
            "lastname": "Chen"
        },
        {
            "affiliation": "Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China.\nWannan Medical College, No. 22, Wenchang West Road, Yijiang District, Wuhu, 241002, China.",
            "firstname": "Wenxin",
            "initials": "W",
            "lastname": "Shao"
        },
        {
            "affiliation": "Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China.\nWannan Medical College, No. 22, Wenchang West Road, Yijiang District, Wuhu, 241002, China.",
            "firstname": "Xingwen",
            "initials": "X",
            "lastname": "Wang"
        },
        {
            "affiliation": "Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China.\nWannan Medical College, No. 22, Wenchang West Road, Yijiang District, Wuhu, 241002, China.",
            "firstname": "Kuo",
            "initials": "K",
            "lastname": "Geng"
        },
        {
            "affiliation": "Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China.\nWannan Medical College, No. 22, Wenchang West Road, Yijiang District, Wuhu, 241002, China.",
            "firstname": "Wenhui",
            "initials": "W",
            "lastname": "Wang"
        },
        {
            "affiliation": "Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China.\nWannan Medical College, No. 22, Wenchang West Road, Yijiang District, Wuhu, 241002, China.",
            "firstname": "Yiming",
            "initials": "Y",
            "lastname": "Li"
        },
        {
            "affiliation": "Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China.\nWannan Medical College, No. 22, Wenchang West Road, Yijiang District, Wuhu, 241002, China.",
            "firstname": "Zhiwei",
            "initials": "Z",
            "lastname": "Liu"
        },
        {
            "affiliation": "Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China. xiehaitang@sina.com.",
            "firstname": "Haitang",
            "initials": "H",
            "lastname": "Xie"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.",
    "doi": "10.1007/s11095-024-03789-w\n10.1016/j.etap.2020.103400\n10.2165/00003088-197702010-00001\n10.1006/phrs.1999.0535\n10.26355/eurrev_202402_35339\n10.1002/psp4.12343\n10.1016/j.clinthera.2015.09.018\n10.1097/00007691-199109000-00001\n10.2165/00003088-199835040-00002\n10.1080/17425255.2019.1685495\n10.1056/nejm199512073332204\n10.1021/acs.biomac.2c00256\n10.1016/j.clpt.2004.02.008\n10.1146/annurev.bi.62.070193.002125\n10.1592/phco.21.9.778.34558\n10.1097/00002030-200002180-00005\n10.1097/00042560-199811010-00001\n10.1097/00002030-200006160-00034\n10.1023/a:1018941328702\n10.1177/0091270004265367\n10.1208/s12248-009-9106-3\n10.1002/cbdv.200590119\n10.1002/psp4.12971\n10.1111/j.2042-7158.2012.01534.x\n10.1016/j.xphs.2020.08.003\n10.1021/acs.molpharmaceut.7b00552\n10.1074/jbc.M110.119248\n10.1023/b:pham.0000026434.82855.69\n10.1097/01.aids.0000183626.74299.77\n10.1007/s13318-022-00765-w\n10.1007/s10928-007-9053-5\n10.1006/faat.1996.0072\n10.1073/pnas.1514240113\n10.1208/s12248-016-0009-9\n10.3389/fphar.2022.1013432\n10.1124/dmd.115.065920\n10.1208/s12248-019-0292-3\n10.1002/cpt.37\n10.1046/j.1365-2125.2003.01824.x\n10.1097/00007691-200406000-00018\n10.1002/jps.23607\n10.1002/mnfr.200700081\n10.1177/0956462416661437\n10.1097/01.aids.0000072673.21517.d6\n10.5414/cpp48192\n10.1124/jpet.102.046532\n10.1056/nejm197905313002202\n10.1073/pnas.0507358102\n10.1016/s0008-6363(02)00767-8\n10.1016/j.ejps.2024.106697",
    "journal": "Pharmaceutical research",
    "keywords": [
        "PK-sim\u00ae",
        "digoxin",
        "drug-drug interaction(DDI)",
        "physiologically-based pharmacokinetic (PBPK) models",
        "ritonavir"
    ],
    "methods": null,
    "publication_date": "2024-11-19",
    "pubmed_id": "39557814\n26975913\n32464466\n322907\n10527640\n38375708\n30091221\n26514315\n1957331\n9812178\n31668105\n7477168\n15229466\n8102521\n11444575\n10716499\n9803961\n10894301\n10468021\n15145962\n19418230\n17191947\n37170680\n22686345\n32791073\n28898584\n20388710\n15180340\n16184031\n9616191\n35486324\n17431751\n8998950\n26951675\n27822600\n36278167\n26296709\n30673891\n25670209\n12848773\n15167636\n23686764\n18214850\n27440872\n12824804\n20197013\n12649369\n431681\n3997300\n16243970\n12650869\n38199444",
    "results": "According to the model simulations, the steady-state exposure of digoxin increased by 86.5% and 90.2% for oral administration, and 80.2% and 90.2% for intravenous administration, respectively, when 0.25\u00a0mg or 0.5\u00a0mg of digoxin was administered concurrently with ritonavir. By reducing the dose of digoxin by 45% or doubling the oral administration interval, similar steady-state concentrations can be achieved compared to when the drugs are not co-administered.",
    "title": "Physiologically Based Pharmacokinetic Modeling to Assess Ritonavir-Digoxin Interactions and Recommendations for Co-Administration Regimens.",
    "xml": "<Element 'PubmedArticle' at 0x788504644630>"
}