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Population Pharmacokinetic Modeling of Secukinumab in Patients With Moderate to Severe Psoriasis
Author(s) -
Bruin Gerard,
Loesche Christian,
Nyirady Judit,
Sander Oliver
Publication year - 2017
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.876
Subject(s) - secukinumab , pharmacokinetics , medicine , volume of distribution , dosing , psoriasis , population , cmin , pharmacology , immunology , cmax , environmental health , psoriatic arthritis
Abstract Secukinumab is a human monoclonal antibody with demonstrated efficacy for moderate to severe psoriasis; it binds to and neutralizes interleukin (IL)‐17A. The pharmacokinetic (PK) parameters of secukinumab were best described by a 2‐compartment model. Only weight was included in the final model, as other covariates did not affect clinical relevance. The estimated serum clearance of secukinumab was 0.19 L/day, with interindividual variability (IIV) of 32% coefficient of variation (CV), and low total volume of distribution (central compartment volume, 3.61 L with IIV of 30% CV; peripheral compartment volume, 2.87 L with IIV of 18% CV). The bioavailability of secukinumab after subcutaneous dosing was approximately 73%, with an absorption rate of 0.18/day with IIV of 35% CV. The PK profile of secukinumab was linear, with no evidence of a dose dependence of clearance. Clearance and volume of secukinumab varied with body weight in an allometric relationship. The time to maximum serum concentration at steady state occurred approximately 6 days after dosing for both secukinumab 300 mg and secukinumab 150 mg. Overall, the PK properties of secukinumab were typical of a 150‐kDa human IgG1 antibody interacting with a soluble target.