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Secukinumab Treatment Does Not Alter the Pharmacokinetics of the Cytochrome P450 3A4 Substrate Midazolam in Patients With Moderate to Severe Psoriasis
Author(s) -
Bruin Gerard,
Hasselberg Anke,
Koroleva Irina,
Milojevic Julie,
Calonder Claudio,
Soon Rachel,
Woessner Ralph,
Pariser David M.,
BoutouyrieDumont Bruno
Publication year - 2019
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1558
Subject(s) - secukinumab , psoriasis , cyp3a4 , pharmacology , pharmacokinetics , medicine , midazolam , cytochrome p450 , blockade , immunology , receptor , metabolism , psoriatic arthritis , sedation
This open‐label disease‐drug–drug interaction study assessed whether blockade of the interleukin ( IL )‐17A pathway by secukinumab and subsequent downregulation of inflammatory cytokines like IL ‐6 or high‐sensitivity C‐reactive protein affects the pharmacokinetics (PKs) of a sensitive probe substrate of the cytochrome P450 3A4 isoform ( CYP 3A4). The PKs of midazolam, metabolized by CYP 3A4, 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. Although demonstrating the expected decrease in downstream inflammatory cytokines, secukinumab had no clinically relevant effects on the PKs of midazolam, provided substantial clinical benefit, and was generally well tolerated. In summary, blockade of IL ‐17A signaling in patients with moderate‐to‐severe psoriasis does not significantly affect CYP 3A4 enzyme activities and, therefore, the use of secukinumab is unlikely to influence the PKs of CYP 3A4 substrates.