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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Diltiazem inhibits human intestinal cytochrome P450 3A ( CYP3A) activity in vivo without altering the expression of intestinal mRNA or protein.

AIMS: To determine the effect of diltiazem on intestinal CYP3A activity and protein and mRNA expression in vivo in healthy subjects. METHODS: Intestinal biopsies were obtained from ten healthy controls and from ten healthy subjects after receiving diltiazem 120 mg bid for 7 days. Intestinal CYP3A activity, CYP3A4 protein and mRNA concentrations were quantified in both groups. Intestinal CYP3A activity was determined by incubation of small bowel homogenate with midazolam (25 microM) and NADPH for 5 min and the rate of formation of 1'-hydroxymidazolam was quantified. RESULTS: All subjects in the treatment group had detectable diltiazem concentration in the serum. While there was no significant difference in CYP3A4 protein and mRNA expression between the control and treatment groups, the formation of 1'-hydroxymidazolam (446 pmol min(-1) mg(-1) 6 (control) vs. 170 (CI 112, 228) pmol min(-1) mg(-1) 95% confidence interval (CI 269, 623) (diltiazem group)) was significantly reduced (P < 0.05). CONCLUSION: Diltiazem decreased small bowel CYP3A activity by 62% as a result of irreversible inhibition with no corresponding change in intestinal CYP3A4 mRNA or protein concentrations.[1]


  1. Diltiazem inhibits human intestinal cytochrome P450 3A (CYP3A) activity in vivo without altering the expression of intestinal mRNA or protein. Pinto, A.G., Horlander, J., Chalasani, N., Hamman, M., Asghar, A., Kolwankar, D., Hall, S.D. British journal of clinical pharmacology. (2005) [Pubmed]
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