Pharmacokinetics of a human monoclonal antibody to IL-12 P40 following single intravenous infusion in patients with moderate to severe plaque-type psoriasis

Abstract

Purpose To assess the pharmacokinetics (PK) of a human monoclonal antibody to IL-12 p40 (anti-IL-12 p40 mAb) following single intravenous (IV) infusion in patients with moderate to severe plaque-type psoriasis as part of a Phase I study. Methods. Patients (n = 18) were randomly assigned to receive a single ascending IV dose of the mAb (n = 4–5 per group). Blood samples were collected and serum mAb levels were measured using an ELISA method. Non-compartmental analysis was employed to calculate the PK parameters of the mAb. The relationship between PK and the severity of psoriatic lesions (Psoriasis Area and Severity Index, PASI) was also investigated to explore the relationship between drug exposure and efficacy. Results. The mAb was slowly eliminated from the circulation after a single IV infusion. The Cmax and AUC were linearly correlated with the dose. Dose-dependent sustained improvements in PASI were observed. Conclusions. PK of the mAb following a single IV infusion were linear and dose-independent, and the systemic exposure increased in a dose-proportional manner. IV administration to patients is feasible in terms of its favorable elimination half-life and sustained clinical response. Clinical Pharmacology & Therapeutics (2004) 75, P9–P9; doi: 10.1016/j.clpt.2003.11.034