Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of humanized monoclonal anti-IL-13 antibodies with different IL-13 neutralization mechanisms

Yulia Vugmeyster, Pamela Szklut, Lioudmila Tchistiakova, William Abraham, Marion Kasaian, Xin Xu

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Numerous animal and in vitro studies suggest that neutralization of IL-13 is an attractive approach for therapeutic intervention in asthma. In this paper we describe preclinical pharmacokinetics (PK), interspecies scaling, and biodistribution of two humanized anti-IL-13 IgG1 monoclonal antibodies, Ab-01 and Ab-02, with different IL-13 neutralization mechanisms. PK parameters of Ab-01 and Ab-02 following IV or SC dosage to mouse, rat, cynomolgus monkey, and sheep, were similar. After IV administration, the elimination of anti-IL-13 antibodies was slow in all species tested and the serum clearance ranged from 0.13 mL/h/kg in monkeys to 0.81 mL/h/kg in mice. Both anti-IL-13 antibodies appeared to be confined primarily to the vascular space, as volume of distribution was relatively small (< 120 mL/kg) in all species and tissue-to-serum concentration ratios (in mice and rats) were low (< 0.5) in the tissues examined. The elimination half-life ranged from 3-6 days in mice to 14-17 days in monkey and sheep. In monkeys, PK parameters appeared to be approximately linear in the 1-100 mg/kg dose range. Following SC administration, the bioavailability of anti-IL-13 antibodies was 60-90% in all species tested. PK profile of Ab-02 in the model of acute airway inflammation (induced by Ascaris challenge) was, in general, similar to that in unchallenged monkeys; however, volume of distribution and clearance tended to decrease in Ascaris-challenged animals. Allometric scaling suggested that anti-IL-13 antibodies would likely to have a favorable PK profile, such as slow clearance and long terminal half-life, following IV or SC administration to humans.

Original languageEnglish (US)
Pages (from-to)477-483
Number of pages7
JournalInternational Immunopharmacology
Volume8
Issue number3
DOIs
StatePublished - Mar 1 2008

Keywords

  • Allergy
  • Allometric scaling
  • Asthma
  • IL-13
  • Monoclonal antibody
  • Pharmacokinetics

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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