An open‐label, single‐dose bioavailability study of the pharmacokinetics of CAT‐354 after subcutaneous and intravenous administration in healthy males
- 10 May 2010
- journal article
- research article
- Published by Wiley in British Journal of Clinical Pharmacology
- Vol. 69 (6), 645-655
- https://doi.org/10.1111/j.1365-2125.2010.03647.x
Abstract
To assess the bioavailability and pharmacokinetics of CAT-354, an anti-IL-13 human monoclonal IgG4 antibody, following subcutaneous (s.c.) and intravenous (i.v.) administration. This was a single-dose, randomized, open-label, parallel-group bioavailability study. Healthy male subjects aged 20-54 years were randomly assigned to one of three dose groups (n= 10/group) to receive CAT-354: 150 mg i.v.; 150 mg s.c. or 300 mg s.c. (two 150 mg injections). Serum pharmacokinetics, adverse events (AEs), vital signs, electrocardiograms and laboratory parameters were assessed. CAT-354 showed bioavailability of 62% and 60% after 150 mg and 300 mg s.c. doses, respectively, and linear pharmacokinetics over the dose range tested. Peak serum concentrations in the s.c. groups occurred after 3-9 (median 5) days, with a mean elimination half-life of 19.2 +/- 3.1 days (150 mg) and 19.4 +/- 3.59 days (300 mg) after s.c. and 21.4 +/- 2.46 days after i.v. administration. Volume of distribution at steady state (V(ss)) was 4960 +/- 1440 ml kg(-1) after i.v. (slightly greater than plasma volume). Average apparent clearances (CL/F) were 292 +/- 82.3 and 307 +/- 109 ml day(-1) after 150 and 300 mg s.c., respectively; systemic CL of 188 +/- 84.0 ml day(-1) after i.v. dosing was consistent with endogenous IgG and reticuloendothelial elimination. No severe or serious AEs occurred. Among 40 reported AEs, 25 were headache, sinus disorders/respiratory symptoms and changes in body temperature perception. CAT-354 exhibited bioavailability of approximately 60% when given s.c. to healthy male subjects.Keywords
This publication has 23 references indexed in Scilit:
- Therapeutics targeting IL-13 for the treatment of pulmonary inflammation and airway remodeling.2008
- Can Guideline-defined Asthma Control Be Achieved?American Journal of Respiratory and Critical Care Medicine, 2004
- Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology productsJournal of Immunological Methods, 2004
- Interleukin‐4 and ‐13 expression is co‐localized to mast cells within the airway smooth muscle in asthmaClinical and Experimental Allergy, 2003
- IL-13 receptors and signaling pathways: An evolving webJournal of Allergy and Clinical Immunology, 2003
- Pharmacokinetic model to describe the lymphatic absorption of r-metHu-leptin after subcutaneous injection to sheep.Pharmaceutical Research, 2003
- TH2 cytokine expression in bronchoalveolar lavage fluid T lymphocytes and bronchial submucosa is a feature of asthma and eosinophilic bronchitisJournal of Allergy and Clinical Immunology, 2002
- Intrinsic Defect in T Cell Production of Interleukin (IL)-13 in the Absence of Both IL-5 and Eotaxin Precludes the Development of Eosinophilia and Airways Hyperreactivity in Experimental AsthmaThe Journal of Experimental Medicine, 2002
- IL-13 induces eosinophil recruitment into the lung by an IL-5– and eotaxin-dependent mechanismJournal of Allergy and Clinical Immunology, 2001
- Predominant TH2-like Bronchoalveolar T-Lymphocyte Population in Atopic AsthmaNew England Journal of Medicine, 1992