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Population Pharmacokinetic Modeling of Secukinumab in Patients With Moderate to Severe Psoriasis

Bruin, Gerardus and Loesche, Christian and Nyirady, Judit and Sander, Oliver (2017) Population Pharmacokinetic Modeling of Secukinumab in Patients With Moderate to Severe Psoriasis. Journal of Clinical Pharmacology, 57 (7). pp. 876-885. ISSN 1552-4604

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.

Item Type: Article
Keywords: IL-17A monoclonal antibody pharmacodynamics population pharmacokinetics psoriasis secukinumab
Date Deposited: 22 Nov 2017 00:45
Last Modified: 25 Jan 2019 00:45
URI: https://oak.novartis.com/id/eprint/28683

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