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Secukinumab treatment does not alter the pharmacokinetics of the CYP3A4 substrate midazolam in patients with moderate to severe psoriasis – results from an open label disease-drug-drug interaction study

Bruin, Gerardus and Hasselberg, Anke and Korolova, Irena and Milojevic, Julie and Calonder, Claudio and Soon, Rachel and Woessner, Ralph and Pariser, David and Boutouyrie-Dumont, Bruno (2019) Secukinumab treatment does not alter the pharmacokinetics of the CYP3A4 substrate midazolam in patients with moderate to severe psoriasis – results from an open label disease-drug-drug interaction study. Clinical pharmacology and therapeutics, Early (Early ).

Abstract

This open-label disease drug–drug interaction study assessed whether blockade of the interleukin (IL)-17A pathway by secukinumab and subsequent down regulation of inflammatory cytokines like IL-6 or high sensitivity c-reactive protein (hsCRP) affects the pharmacokinetics of a senstive probe substrate of the cytochrome P450 3A4 isoform (CYP3A4). The pharmacokinetics of midazolam, metabolized by CYP3A4, was evaluated before and after 7 and 35 days of treatment initiation of subcutaneous secukinumab at a dose of 300 mg weekly in 24 patients with moderate-to-severe psoriasis. While demonstarting the expected decrease in downstream inflammatory cytokines, secukinumab had no clinically relevant effects on the pharmacokinetics of midazolam, provided substantial clinical benefit, and was generally well tolerated.
In summary, blockade of IL-17A signaling in moderate to severe psoriasis patients does not significantly affect CYP3A4 enzyme activities and therefore the use of secukinumab is unlikely to influence the pharmacokinetics of CYP3A4 substrates.

Item Type: Article
Keywords: secukinumab, monoclonal antibody, disease-drug-drug interactions, psoriasis, midazolam, CYP3A4
Date Deposited: 13 Nov 2019 00:45
Last Modified: 13 Nov 2019 00:45
URI: https://oak.novartis.com/id/eprint/39307

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