Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
International Journal of Toxicology
This Article
Right arrow Full Text (PDF)
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Kung, A. H. C.
Right arrow Articles by White, M. L.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Kung, A. H. C.
Right arrow Articles by White, M. L.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Continuous Infusion Animal Model for the Immunoconjugate Xomazyme-CD5 Plus, in the Rat

Ada H. C. Kung

Department of Toxicology and Pharmacology, XOMA Corporation, Berkeley, California, U.S.A.

Kellie N. Kong

Department of Toxicology and Pharmacology, XOMA Corporation, Berkeley, California, U.S.A.

Kirsten A. Achilles

Department of Toxicology and Pharmacology, XOMA Corporation, Berkeley, California, U.S.A.

Virginia L. Mohler

Department of Toxicology and Pharmacology, XOMA Corporation, Berkeley, California, U.S.A.

Mark L. White

Department of Clinical Pathology, XOMA Corporation, Berkeley, California, U.S.A.

The immunoconjugate, XomaZyme-CD5 Plus, consists of a murine immunoglobulin IgGl monoclonal antibody directed against the CD5 antigen present on mature human T lymphocytes and ricin A chain (RTA), a potent ribosomal inhibitory protein. XomaZyme-CD5 Plus, administered as an 1-hour infusion, has shown efficacy in patients with steroid-resistant acute graft versus host disease. An animal model was developed to study the toxicity profile of XomaZyme-CD5 Plus when administered by continuous intravenous infusion in the rat and to support the delivery of the drug by this method in human clinical trials. This animal model involved the continuous i.v. infusion of XomaZyme-CD5 Plus in conscious rats for 10 consecutive days via catheterization of the external jugular vein and surgical attachment of the animals to a tether/swivel system leading to a syringe pump. In addition, a comparison study was conducted with XomaZyme-CD5 Plus administered to rats at the same daily dose by bolus i.v. injection for 10 days. Qualitatively similar toxicity profiles were observed for XomaZyme-CD5 Plus given by bolus injection and by continuous infusion in rats. Comparing equivalent dose levels, 0.5 mg/kg/day, XomaZyme-CD5 Plus given by continuous i.v. infusion was similar in toxicity as given by bolus injection. The anti-immunoconjugate (XomaZyme-CD5 Plus) antibody response occurred later and titers were lower after infusion in comparison to bolus injection. We have demonstrated that the rat continuous i.v. infusion model can be successfully used to deliver protein therapeutics at accurate dosages to study standard acute to subchronic toxicity profiles.

Key Words: Continuous infusion • Rat • Monoclonal antibody • Immunoconjugate

International Journal of Toxicology, Vol. 13, No. 1, 64-75 (1994)
DOI: 10.3109/10915819409140656
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?