title: Population Pharmacokinetic Modeling of Secukinumab in Patients With Moderate to Severe Psoriasis.
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.
authors.affiliation: Novartis Pharma AG, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Gerard
authors.initials: G
authors.lastname: Bruin
authors.affiliation: Novartis Pharma AG, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Loesche
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Judit
authors.initials: J
authors.lastname: Nyirady
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Sander
mesh_terms: D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D006801:Humans; D020381:Interleukin-17; D008954:Models, Biological; D011565:Psoriasis / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D020381:Interleukin-17; C555450:secukinumab
keywords: IL-17A; monoclonal antibody; pharmacodynamics; population pharmacokinetics; psoriasis; secukinumab