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Interleukin-6 and cytochrome-P450, reason for concern?
Sooha Kim1, Andrew J K Östör, Muhammad K Nisar
1School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Rheumatology International
|March 28, 2012
Summary
Tocilizumab (TCZ) reverses IL-6
Area of Science:
- Pharmacology
- Immunology
- Drug Metabolism
Background:
- Rheumatoid arthritis (RA) pathogenesis involves Interleukin-6 (IL-6).
- Tocilizumab (TCZ), an anti-IL-6 receptor antibody, treats RA.
- IL-6 downregulates cytochrome P450 (CYP) enzymes, affecting drug metabolism.
Purpose of the Study:
- To systematically review the interaction between TCZ and CYP-metabolized drugs.
- To evaluate the impact of TCZ on CYP enzyme activity and drug bioavailability.
Main Methods:
- Systematic literature review of studies mentioning TCZ and CYP.
- Inclusion of in vitro, in vivo, clinical trials, and reviews.
- Screening based on full-text review for IL-6, TCZ, and CYP interactions.
Main Results:
- TCZ reversed IL-6-induced reduction of CYP isozymes (CYP3A4, CYP2C9, CYP2C19) in vitro.
- TCZ reduced bioavailability of simvastatin (CYP3A4 substrate) and omeprazole (CYP2C19 substrate) in vivo.
- Dextromethorphan (CYP2D6/CYP3A4 substrate) bioavailability was unaffected by TCZ.
Conclusions:
- TCZ increases CYP isozyme activity, clinically relevant due to decreased drug bioavailability.
- Caution advised when co-prescribing TCZ with CYP-metabolized drugs, especially CYP3A4 substrates.
- Further research is needed to fully elucidate TCZ-CYP interactions.
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