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Depression of Drug‐metabolizing Activity in the Human Liver by Interferon‐β
Author(s) -
Okuno Hiroyasu,
Takasu Masashi,
Kano Haruhiko,
Seki Toshihito,
Shiozaki Yasuko,
Inoue Kyoichi
Publication year - 1993
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840170113
Subject(s) - theophylline , pharmacokinetics , interferon , volume of distribution , medicine , pharmacology , hepatitis , endocrinology , chemistry , immunology
Abstract The depressant effect of interferon beta on drugmetabolizing activity in the human liver was investigated. Seven patients with chronic hepatitis C were treated with interferon beta at doses of 3 × 10 6 to 9 × 10 6 IU/day for 8 wk. The activities of 7‐methoxycoumarin O‐demethylase and 7‐ethoxycoumarin O‐deethylase in specimens obtained by liver biopsy were examined before and after interferon treatment. Theophylline pharmacokinetics were also examined before and after interferon treatment. Interferon beta treatment reduced the activities of both O‐dealkylases from 6.0 (100%) to 3.2 (53%) nmol/gm liver per minute and from 1.9 (100%) to 1.1 (58%) nmol/gm liver per minute, respectively (p < 0.05). The total body clearance of theophylline was also decreased (from 0.76 to 0.56 ml/kg/min; p < 0.05), and its elimination half‐life was increased (from 8.4 to 11.7 hr; p < 0.05); however, the volume of distribution was not significantly affected. The magnitude of the decreases in enzyme activities and in theophylline clearance varied widely in individual patients and did not correlate with the dose of interferon administered. This study provides the first direct evidence that interferon beta can depress the activity of drugmetabolizing enzymes in the human liver. (H EPATOLOGY 1993;17:65–69.)