Bruin, Gerardus, Loesche, Christian, 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