Pharmacokinetics and pharmacodynamics of SB-240563, a humanized monoclonal antibody directed to human interleukin-5, in mild asthmatics

Abstract

Clinical Pharmacology & Therapeutics (1999) 65, 147–147; doi:

Pharmacokinetic and Pharmacodynamic Modeling of a Humanized Anti-IL-13 Antibody in Naive and Ascaris-Challenged Cynomolgus Monkeys

“…The Ab-02 PK parameters estimated by PK-PD modeling were consistent with those estimated by non-compartmental analysis (20). Ab-02 had a low clearance and a small volume of distribution in monkeys, typical of those seen for other humanized IgG1 therapeutic proteins (29)(30)(31). The PK-PD modeling further confirmed that Ab-02 volume of distribution was smaller in Ascaris-challenged monkeys when compared a For estimation of mean parameters in naive animals, three animals in the 1 mg/kg, IV group and two animals in the 2 mg/kg, SC group were used.…”

Anti–IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels

“…Indeed, a smaller clinical trial with another humanized anti-IL-5 antibody (reslizumab) has suggested that rebound eosinophilia might be related to subsequent overproduction of IL-5. 19,34 Mepolizumab has a half-life of 13 ± 2 days after intravenous administration, 35 but its biologic activity can be longer, as observed by the significant decrease in peripheral blood eosinophil levels that persisted for 3 months in 76% of subjects after the final mepolizumab infusion. Interestingly, in 33% of subjects, a partial to complete recovery of peripheral blood eosinophil levels (an increase of 50% or greater) was observed at week 28, approaching levels observed at week 8; an even greater effect on eosinophil levels was observed when corticosteroid therapy was decreased.…”

Preclinical efficacy and safety of pascolizumab (SB 240683): a humanized anti-interleukin-4 antibody with therapeutic potential in asthma

“…The presence of pascolizumab in monkey plasma was determined using a selective electrogenerated chemiluminescence immunoassay similar to that described previously [16]. The lower limit of detection for pascolizumab was 50 ng/ml.…”