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The ratios (R<jats:sub>AUC<\/jats:sub>) of total area under the curve (AUC) for MDZ with inhibitor divided by MDZ AUC in the control condition were aggregated across individual studies for each inhibitor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mean (\u00b1 SE) R<jats:sub>AUC<\/jats:sub> values were: ketoconazole (15 studies, 131 subjects), 11.5 (\u00b11.2); itraconazole (five studies, 48 subjects), 7.3 (\u00b11.0); clarithromycin (five studies, 73 subjects), 6.5 (\u00b110.9); and ritonavir (13 studies, 159 subjects), 14.5 (\u00b12.0). Differences among inhibitors were significant (<jats:italic>F<\/jats:italic> = 5.31, <jats:italic>P<\/jats:italic> &lt; 0.005). R<jats:sub>AUC<\/jats:sub> values were not significantly related to inhibitor dosage or to duration of inhibitor pre\u2010exposure prior to administration of MDZ.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ritonavir produces CYP3A inhibition equivalent to or greater than ketoconazole, and is the best index CYP3A inhibitor alternative to ketoconazole. Cobicistat closely resembles ritonavir in structure and function, and can also be considered. Itraconazole and clarithromycin are not suitable alternatives since they do not produce inhibition comparable with ketoconazole or ritonavir, and have other significant disadvantages as well.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12668","type":"journal-article","created":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T18:28:02Z","timestamp":1430245682000},"page":"342-350","source":"Crossref","is-referenced-by-count":100,"title":["Ritonavir is the best alternative to ketoconazole as an index inhibitor of cytochrome P450\u20103A in drug\u2013drug interaction studies"],"prefix":"10.1111","volume":"80","author":[{"given":"David J.","family":"Greenblatt","sequence":"first","affiliation":[{"name":"From the Program in Pharmacology and Experimental Therapeutics Tufts University School of Medicine and Sackler School of Graduate Biomedical Sciences  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerold S.","family":"Harmatz","sequence":"additional","affiliation":[{"name":"From the Program in Pharmacology and Experimental Therapeutics Tufts University School of Medicine and Sackler School of Graduate Biomedical Sciences  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"FDADrug Safety Communication: FDA limits usage of Nizoral (ketoconazole) oral tablets due to potentially fatal liver injury and risk of drug interactions and adrenal gland problems. 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