Summary
The depressant effect of interferon-α 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-α can impair the activity of drug metabolizing enzymes in the human liver.
Article PDF
Similar content being viewed by others
References
Chang KC, Bell TD, Lauer BA, Chai H (1978) Altered theophylline pharmacokinetics during acute respiratory viral illness. Lancet I: 1132–1133
Renton KW, Gray JD, Hall RI (1980) Decreased elimination of theophylline after influenza vaccination. Can Med Assoc J 123: 288–290
Gray JD, Renton KW, Hung OR (1983) Depression of theophylline elimination following BCG vaccination. Br J Clin Pharmacol 16: 735–737
Renton KW, Mannering GJ (1976) Depression of hepatic cytochrome P-450-dependent monooxygenase systems with administered interferon inducing agents. Biochem Biophys Res Commun 73: 343–348
Mannering GJ, Renton KW, El Azhary R, Deloria LB (1980) Effects of interferon-inducing agents on hepatic cytochrome P-450 drug metabolizing systems. Ann NY Acad Sci 350: 314–331
Singh G, Renton KW, Stebbing N (1982) Homogenous interferon from E. coli depresses hepatic cytochrome P-450 and drug biotransformation. Biochem Biophys Res Commun 106: 1256–1261
Parkinson A, Lasker J, Kramer MJ, Huang M, Thomas PE, Ryan DE, Peik LM, Norman RL, Levin W, Conney AH (1982) Effects of three recombinant human leukocyte interferons on drug metabolism in mice. Drug Metab Dispos 10: 579–585
Renton KW, Singh G, Stebbing N (1984) Relationship between the antiviral effects of interferons and their abilities to depress cytochrome P-450. Biochem Pharmacol 33: 3899–3902
Williams SJ, Farrell GC (1986) Inhibition of antipyrine metabolism by interferon. Br J Clin Pharmacol 22: 610–612
Williams SJ, Baird-Lambert JA, Farrell GC (1987) Inhibition of theophylline metabolism by interferon. Lancet II: 939–941
Ullrich V, Weber P (1972) The O-dealkylation of 7-ethoxycoumarin by liver microsomes: A direct fluorometric test. Hoppe Seylers Z Physiol Chem 353: 1171–1177
Gooderham NJ, Mannering GJ (1986) Depression of cytochrome P-450 and alterations of protein metabolism in mice treated with the interferon inducer polyriboinosinic acid polyribocytidylic acid. Arch Biochem Biophys 250: 418–425
Ghezzi P, Saccardo B, Bianchi M (1986) Induction of xanthine oxidase and heme oxygenase and depression of liver drug metabolism by interferon: A study with different recombinant interferons. J Interferon Res 6: 251–256
Shindo M, Okuno T, Matsumoto M, Takeda M, Takino T, Sokawa J, Iwata A, Sokawa Y (1988) Serum 2′,5′-oligoadenylate synthetase activity during interferon treatment of chronic hepatitis B. Hepatology 8: 366–370
Koren HS, Brandt CP, Tso CY, Laszlo J (1983) Modulation of natural killing activity by lymphoblastoid interferon in cancer patients. J Biol Resp Modif 2: 151–165
Rhodes J, Jones DH, Bleehen NM (1983) Increased expression of human monocyte HLA-DR antigens and Fcγ receptors in response to human interferon in vivo. Clin Exp Immunol 53: 739–743
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Okuno, H., Kitao, Y., Takasu, M. et al. Depression of drug metabolizing activity in the human liver by interferon-α. Eur J Clin Pharmacol 39, 365–367 (1990). https://doi.org/10.1007/BF00315411
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00315411