Continuous Infusion Animal Model for the Immunoconjugate Xomazyme-CD5 Plus, in the Rat
| Autor: | Mark L. White, Ada H. C. Kung, Virginia L. Mohler, Kellie N. Kong, Kirsten A. Achilles |
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| Rok vydání: | 1994 |
| Předmět: |
Syringe driver
Pathology medicine.medical_specialty biology business.industry 030206 dentistry Pharmacology Toxicology 030226 pharmacology & pharmacy Immunoconjugate 03 medical and health sciences 0302 clinical medicine Bolus (medicine) Antigen Toxicity medicine biology.protein Antibody business Perfusion External jugular vein |
| Zdroj: | Journal of the American College of Toxicology. 13:64-75 |
| ISSN: | 0730-0913 |
| DOI: | 10.3109/10915819409140656 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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