期刊
ARCHIVES OF PHARMACAL RESEARCH
卷 40, 期 12, 页码 1356-1379出版社
PHARMACEUTICAL SOC KOREA
DOI: 10.1007/s12272-017-0976-0
关键词
Physiologically based pharmacokinetic modeling; Drug-drug interaction; Prediction
资金
- Bio & Medical Technology Development Program through the National Research Foundation of Korea grant - Ministry of Education, Korea [2013M3A9B5075838]
- Basic Research Laboratory (BRL) Program through the National Research Foundation of Korea grant - Ministry of Education, Korea [2015R1A4A1042350]
- National Research Foundation of Korea [2013M3A9B5075838] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The occurrence of drug-drug interactions (DDIs) can significantly affect the safety of a patient, and thus assessing DDI risk is important. Recently, physiologically based pharmacokinetic (PBPK) modeling has been increasingly used to predict DDI potential. Here, we present a PBPK modeling concept and strategy. We also surveyed PBPK-related articles about the prediction of DDI potential in humans published up to October 10, 2017. We identified 107 articles, including 105 drugs that fit our criteria, with a gradual increase in the number of articles per year. Studies on antineoplastic and immunomodulatory drugs (26.7%) contributed the most to published PBPK models, followed by cardiovascular (20.0%) and anti-infective (17.1%) drugs. Models for specific products such as herbal products, therapeutic protein drugs, and antibody-drug conjugates were also described. Most PBPK models were used to simulate cytochrome P450 (CYP)-mediated DDIs (74 drugs, of which 85.1% were CYP3A4-mediated), whereas some focused on transporter-mediated DDIs (15 drugs) or a combination of CYP and transporter-mediated DDIs (16 drugs). Full PBPK, first-order absorption modules and Simcyp(A (R)) software were predominantly used for modeling. Recently, DDI predictions associated with genetic polymorphisms, special populations, or both have increased. The 107 published articles reasonably predicted the DDI potentials, but further studies of physiological properties and harmonization of in vitro experimental designs are required to extend the application scope, and improvement of DDI predictions using PBPK modeling will be possible in the future.
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