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We evaluated the effects of 30 anti-TB drugs, novel candidates, macrolides, and representative antiretroviral drugs on human CYP3A4 activity using a commercially available screening kit for CYP3A4 inhibitors and a human hepatocyte, HepaRG. Moreover, in order to estimate the interactions of these drugs with human P-gp, screening for substrates was performed. For some substrates, P-gp inhibition tests were carried out using P-gp-expressing MDCK cells. As a result, almost all the compounds showed the expected effects on human CYP3A4 both in the<jats:italic>in vitro<\/jats:italic>screening and in HepaRG cells. Importantly, the unproven mechanisms of DDIs caused by WHO group 5 drugs, thioamides, and<jats:italic>p<\/jats:italic>-aminosalicylic acid were elucidated. Intriguingly, clofazimine (CFZ) exhibited weak inductive effects on CYP3A4 at &gt;0.25 \u03bcM in HepaRG cells, while an inhibitory effect was observed at 1.69 \u03bcM in the<jats:italic>in vitro<\/jats:italic>screening, suggesting that CFZ autoinduces CYP3A4 in the human liver. Our method, based on one of the pharmacokinetics parameters in humans, provides more practical information associated with not only DDIs but also with drug metabolism.<\/jats:p>","DOI":"10.1128\/aac.02278-13","type":"journal-article","created":{"date-parts":[[2014,3,25]],"date-time":"2014-03-25T05:38:21Z","timestamp":1395725901000},"page":"3168-3176","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["Comparative Study of the Effects of Antituberculosis Drugs and Antiretroviral Drugs on Cytochrome P450 3A4 and P-Glycoprotein"],"prefix":"10.1128","volume":"58","author":[{"given":"Yasuhiro","family":"Horita","sequence":"first","affiliation":[{"name":"Department of Pathophysiology and Host Defense, Japan Anti-Tuberculosis Association, Research Institute of Tuberculosis, Kiyose, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norio","family":"Doi","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Host Defense, Japan Anti-Tuberculosis Association, Research Institute of Tuberculosis, Kiyose, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4001"},{"key":"e_1_3_3_3_2","volume-title":"Global tuberculosis report 2012","author":"World Health Organization","year":"2012","unstructured":"World Health Organization. 2012. 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