Cytochrome P450-mediated interactions of monoclonal antibodies and small-molecules drugs

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Immunologically active proteins such as interferons, interleukins (IL-1, IL-6, IL-10), various ligands (e.g., tumor necrosis factor alpha) which are produced in mammals in response to infectious or inflammatory processes can inhibit the activity of CYP450 enzymes. This interaction can result in an increase of CYP450-substrates levels and toxic effects of treatment. The use of cytokines as biological drugs also can affect the pharmacokinetics of co-administered medications. On the other hand, a decrease in the cytokines levels induced by monoclonal antibodies can restore liver enzyme activity that may be inhibited during infection or inflammation. This effect can lead to reduced effectiveness of the co-administered drugs that are CYP450 substrates due to the acceleration of drugs metabolism and decrease in their concentration. The article reviews the recent studies of CYP450-mediated interactions between monoclonal antibodies targeting various cytokines and small molecule drugs.

Key words

Monoclonal antibodies, small molecule drugs, drug-drug interaction, cytochrome P450, pro-inflammatory cytokines, cytokine modulators.