Population Pharmacokinetic Modeling of Secukinumab in Patients With Moderate to Severe Psoriasis. (8th March 2017)

• Record Type: Journal Article
• Authors: Bruin, Gerard; Loesche, Christian; Nyirady, Judit; Sander, Oliver
• Is Part Of: Journal of clinical pharmacology. Volume 57:Number 7(2017)
• Page Start: 876
• Page End: 885
• Publication Date: 2017-03-08
• Subjects: IL‐17A -- monoclonal antibody -- pharmacodynamics -- population pharmacokinetics -- psoriasis -- secukinumab; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.876
• Languages: English
• ISSNs: 0091-2700

Abstract

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.