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CYP-Mediated Therapeutic Protein-Drug Interactions

Clinical Findings, Proposed Mechanisms and Regulatory Implications

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Abstract

Therapeutic proteins (TPs) may affect the disposition of drugs that are metabolized by cytochrome P450 (CYP) enzymes, as is evident from a review of data in recently published literature and approved Biologic License Applications. Many TPs belonging to the cytokine class appear to differentially affect CYP activities. Cytokine modulators may affect CYP enzyme activities by altering cytokine effects on CYP enzymes. The alteration in CYP enzyme activities seems to result from changes in transcription factor activity for CYP enzyme expression or changes in CYP enzyme stability, which have been observed during altered immunological states such as infection and inflammation. Human growth hormone also appears to differentially affect CYP activities through unknown mechanisms. Because TP-drug interaction research is an evolving area, limited information is available during drug development on TP-drug interactions mediated by CYP inhibition or induction. The authors of this review suggest that effort be made to understand TP-drug interactions for the safe and effective use of TPs in combination with small-molecule drugs.

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Acknowledgements

The authors express special thanks to Drs. Hong Zhao and Nam Atiqur Rahman for their valuable comments in the preparation of this article. The authors have no conflicts of interest that are directly relevant to the content of this review. No sources of funding were used to assist in the preparation of this review.

The views presented in this article are those of authors and do not necessarily reflect the official position of the United States Food and Drug Administration.

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Correspondence to Jang-Ik Lee.

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Lee, JI., Zhang, L., Men, A.Y. et al. CYP-Mediated Therapeutic Protein-Drug Interactions. Clin Pharmacokinet 49, 295–310 (2010). https://doi.org/10.2165/11319980-000000000-00000

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