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

Induction of multidrug resistance-1 and cytochrome P450 mRNAs in human mononuclear cells by rifampin.

Reverse transcription-polymerase chain reaction (RT-PCR) and quantitative, competitive RT-PCR were used to examine the capability of rifampin to induce the expression of mRNA derived from multidrug resistance-1 (MDR1) and drug-metabolizing cytochrome P450 (P450) genes in the mononuclear fraction (lymphocytes) of human blood. A total of 50 healthy volunteers (age, 18-74) participated in two studies in which 600 mg of rifampin was administered orally once daily in the evening for 7 days. Twenty of these individuals also received fexofenadine before and after rifampin dosing. MDR1 and CYP2C8 mRNAs were expressed in 100% (50 of 50) and 95% (35 of 37) of individuals, respectively, at baseline. A significant (P < 0.05; n = 37) increase in the expression of MDR1 mRNA from 176,900 +/- 122,000 to 248,500 +/- 162,300 molecules/microg of RNA was observed following rifampin administration in the human lymphocytes. There was no significant (P > 0.05) difference in MDR1 mRNA expression between males and females at baseline. Interestingly, 58% of the individuals (n = 29) demonstrated a 120% increase [95% confidence interval (CI); 120%; range, 81-153%; responders] in MDR1 mRNA expression. In contrast, the remaining 42% of individuals (n = 21) exhibited a mean decrease of -5.2% (95% CI; -5.2%; range, -15 to +4%; nonresponders). Rifampin steady-state trough serum concentrations were not significantly different (P > 0.05) between responders and nonresponders. Likewise, there was no relationship between the observed induction in MDR1 mRNA expression in lymphocytes and the observed increase in fexofenadine oral clearance in twenty volunteers. The mRNA of CYP2E1, CYP3A5, CYP3A7, CYP4A11, and CYP4B1 genes were variably expressed at baseline and following rifampin treatment. In contrast, CYP2C9 and CYP3A4 mRNAs were undetectable in lymphocytes both before and after rifampin dosing. Interindividual variability in baseline expression and inducibility of MDR1 and P450 mRNA in human lymphocytes appeared to be substantial and may not reflect the expression of these enzymes in other tissues.[1]


  1. Induction of multidrug resistance-1 and cytochrome P450 mRNAs in human mononuclear cells by rifampin. Asghar, A., Gorski, J.C., Haehner-Daniels, B., Hall, S.D. Drug Metab. Dispos. (2002) [Pubmed]
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