Volume 17, Issue 2 pp. 230-235

Original Article

Free Access

Interferon suppresses erythromycin metabolism in rats and human subjects

Philip I. Craig,

Philip I. Craig

Department of Medicine, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145, Australia

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Michael Tapner,

Michael Tapner

Department of Medicine, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145, Australia

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Geoffrey C. Farrell,

Corresponding Author

Geoffrey C. Farrell

Associate Professor

Department of Medicine, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145, Australia

Department of Medicine, Westmead Hospital, Westmead NSW 2145, Australia===Search for more papers by this author

Philip I. Craig,

Philip I. Craig

Department of Medicine, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145, Australia

Search for more papers by this author

Michael Tapner,

Michael Tapner

Department of Medicine, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145, Australia

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Geoffrey C. Farrell,

Corresponding Author

Geoffrey C. Farrell

Associate Professor

Department of Medicine, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145, Australia

Department of Medicine, Westmead Hospital, Westmead NSW 2145, Australia===Search for more papers by this author

First published: February 1993

https://doi.org/10.1002/hep.1840170212

Citations: 44

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Abstract

Interferon down-regulates expression of cytochrome P-450 3A in male rats. This study explored the hypothesis that interferon therefore decreases the metabolism of drugs catalyzed by cytochrome P-450 3A. Initial experiments in male rats used microsomal erythromycin N-demethylase activity as a probe for cytochrome P-450 3A catalytic activity. After administration of rat interferon-γ, erythromycin metabolism was impaired (53% of control; p < 0.01). This change correlated with the decline in cytochrome P-450 3A–dependent androstenedione 6β-hydroxylase activity, indicating that the decrease in erythromycin N-demethylase activity could be attributed to interferon-mediated suppression of cytochrome P-450 3A. We then used the [¹⁴C]N-methyl erythromycin breath test to assess the activity of hepatic cytochrome P-450 3A in rats and human subjects before and after a single dose of interferon. In rats, rat interferon-γ decreased erythromycin metabolism to 57% of control (p < 0.005). In the human study, six patients with chronic active hepatitis C and four healthy controls were examined 20 to 26 hr after receiving a subcutaneous injection of human interferon-α_2b. Interferon produced a small decrease (median = 15%; range = 3% to 35%) in erythromycin metabolism (p < 0.05), as determined by 2-hr excretion of ¹⁴CO₂ in the breath. Thus interferon-mediated suppression of cytochrome P-450 3A is less strong in human subjects than in male rats. Comparison of our data about the effect of interferon on cytochrome P-450 3A activity with earlier observations of a major impairment of theophylline clearance in human beings suggests that in human subjects interferon may have a more important effect on other drug-metabolizing enzymes, such as those of the cytochrome P-450 1A subfamily. However, interferon may produce clinically relevant impairment in the elimination of drugs that are substrates for cytochrome P-450 3A, should such agents have a narrow therapeutic index. (HEPATOLOGY 1993;17:230–235.)

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Volume17, Issue2

February 1993

Pages 230-235

Interferon suppresses erythromycin metabolism in rats and human subjects

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Interferon suppresses erythromycin metabolism in rats and human subjects

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