Depression of drug metabolizing activity in the human liver by interferon-alpha.
The depressant effect of interferon-alpha on drug metabolizing activity in the liver has been investigated in 12 patients with chronic active hepatitis B. 7-methoxy-coumarin (7-MC) O-demethylase and 7-ethoxycoumarin (7-EC) O-deethylase, in specimens obtained by liver biopsy, were measured before and after interferon treatment. 7-MC and 7-EC O-dealkylase activity were significantly reduced after interferon treatment, from 13.4 to 9.24 nmol.g-1 liver.min-1, and from 3.22 to 2.16 nmol.g-1 liver.min-1, respectively. The magnitude of the fall varied widely between individual patients. The study provides the first direct evidence that interferon-alpha can impair the activity of drug metabolizing enzymes in the human liver.
Okuno
H
H
Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Kitao
Y
Y
Takasu
M
M
Kano
H
H
Kunieda
K
K
Seki
T
T
Shiozaki
Y
Y
Sameshima
Y
Y
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D002908:Chronic Disease; D005260:Female; D006509:Hepatitis B / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010090:Oxidoreductases, O-Demethylating / Q000378:metabolism*
D007370:Interferon Type I; C047335:7-methoxycoumarin-O-demethylase; D010090:Oxidoreductases, O-Demethylating; D015660:7-Alkoxycoumarin O-Dealkylase