{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:08:49Z","timestamp":1791050929497,"version":"4.1.0"},"reference-count":0,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2002,6,17]],"date-time":"2002-06-17T00:00:00Z","timestamp":1024272000000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2002,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Interferon \u03b1 (IFN\u2010\u03b1) is thought to be responsible for cytochrome P450 (CYP)\u2010dependent drug interactions mediated by a decrease in CYP activities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The objectives are to determine whether IFN\u2010\u03b1 and ribavirin can alter pretreatment CYP1A2, CYP2D6, CYP3A4 and <jats:italic>N<\/jats:italic>\u2010acetyltransferase\u20102 activities after 1 month of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Enzymatic activities were determined among 14 patients with chronic active hepatitis C before IFN\u2010\u03b1 (3 \u00b7 10<jats:sup>6<\/jats:sup> U, 3 times a week) and ribavirin introduction and after 1 month of treatment. During both study periods, subjects received 80 mg dextromethorphan and 140 mg caffeine (1,3,7\u2010trimethylxanthine [137X]). CYP3A4, CYP2D6, and NAT2 activities were assessed by use of urinary metabolic ratios of 3\u2010methoxymorphinan\/dextromethorphan, dextrorphan\/dextromethorphan, and 5\u2010acetylamino\u20106\u2010formylamino\u20103\u2010methyluracil (AFMU)\/1\u2010methylxanthine(1X). The plasma paraxanthine\/caffeine ratio was used to measure CYP1A2 activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CYP3A4 and CYP2D6 activities tended to increase after 1 month of antiviral therapy, but the change did not reach statistical significance. CYP1A2 and NAT2 activities were not significantly modified after 1 month of antiviral treatment. Pretreatment activities were significantly lower than those previously observed in healthy volunteers for CYP2D6 (mean \u00b1 SD, 148 \u00b1 139 versus 759 \u00b1 692; <jats:italic>P<\/jats:italic> = .0008) and CYP3A4 (0.18 \u00b1 0.06 versus 0.52 \u00b1 0.72; <jats:italic>P<\/jats:italic> = .0006). This difference was no longer statistically significant after 1 month of treatment, because CYP2D6 and CYP3A4 activities improved in 7 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients with chronic hepatitis C, pretreatment CYP3A4 and CYP2D6 activities were significantly lower than those observed in healthy volunteers. These differences disappeared after 1 month of antiviral treatment because of the restoration of these CYP activities in about half of the patients.<\/jats:p><jats:p><jats:italic>Clinical Pharmacology &amp; Therapeutics<\/jats:italic> (2002) <jats:bold>71<\/jats:bold>, 488\u2013495; doi: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1067\/mcp.2002.124468\">10.1067\/mcp.2002.124468<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1067\/mcp.2002.124468","type":"journal-article","created":{"date-parts":[[2002,10,9]],"date-time":"2002-10-09T21:24:11Z","timestamp":1034198651000},"page":"488-495","source":"Crossref","is-referenced-by-count":39,"title":["Effect of interferon \u03b1\u2010ribavirin bitherapy on cytochrome P450 1A2 and 2D6 and <i>N<\/i>\u2010acetyltransferase\u20102 activities in patients with chronic active hepatitis C"],"prefix":"10.1111","volume":"71","author":[{"given":"Laurent","family":"Becquemont","sequence":"first","affiliation":[{"name":"Departments of Pharmacology and Hepatology and the Clinical Investigation Center Saint\u2010Antoine University Hospital  Paris"},{"name":"UA 2679, Facult\u00e9 de M\u00e9decine de Lille  Lille"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Chazouilleres","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Hepatology and the Clinical Investigation Center Saint\u2010Antoine University Hospital  Paris"},{"name":"UA 2679, Facult\u00e9 de M\u00e9decine de Lille  Lille"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Serfaty","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Hepatology and the Clinical Investigation Center Saint\u2010Antoine University Hospital  Paris"},{"name":"UA 2679, Facult\u00e9 de M\u00e9decine de Lille  Lille"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Marie","family":"Poirier","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Hepatology and the Clinical Investigation Center Saint\u2010Antoine University Hospital  Paris"},{"name":"UA 2679, Facult\u00e9 de M\u00e9decine de Lille  Lille"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Broly","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Hepatology and the Clinical Investigation Center Saint\u2010Antoine University Hospital  Paris"},{"name":"UA 2679, Facult\u00e9 de M\u00e9decine de Lille  Lille"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Jaillon","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Hepatology and the Clinical Investigation Center Saint\u2010Antoine University Hospital  Paris"},{"name":"UA 2679, Facult\u00e9 de M\u00e9decine de Lille  Lille"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul","family":"Poupon","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Hepatology and the Clinical Investigation Center Saint\u2010Antoine University Hospital  Paris"},{"name":"UA 2679, Facult\u00e9 de M\u00e9decine de Lille  Lille"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Funck\u2010Brentano","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Hepatology and the Clinical Investigation Center Saint\u2010Antoine University Hospital  Paris"},{"name":"UA 2679, Facult\u00e9 de M\u00e9decine de Lille  Lille"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,6,17]]},"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1067\/mcp.2002.124468","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T08:50:21Z","timestamp":1700297421000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1067\/mcp.2002.124468"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,6]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2002,6]]}},"alternative-id":["10.1067\/mcp.2002.124468"],"URL":"https:\/\/doi.org\/10.1067\/mcp.2002.124468","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,6]]}}}