Interferon suppresses erythromycin metabolism in rats and human subjects

Hepatology. 1993 Feb;17(2):230-5.


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-gamma, erythromycin metabolism was impaired (53% of control; p < 0.01). This change correlated with the decline in cytochrome P-450 3A-dependent androstenedione 6 beta-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-gamma 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-alpha 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Chronic Disease
  • Erythromycin / metabolism*
  • Female
  • Hepatitis C / metabolism
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / pharmacology
  • Interferons / pharmacology*
  • Male
  • Middle Aged
  • Rats
  • Rats, Wistar
  • Recombinant Proteins
  • Reference Values


  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Erythromycin
  • Interferons