Pharmacokinetics and antibody responses to the CD3 antibody otelixizumab used in the treatment of type 1 diabetes
| العنوان: | Pharmacokinetics and antibody responses to the CD3 antibody otelixizumab used in the treatment of type 1 diabetes |
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| المؤلفون: | Evy Vandemeulebroucke, Peppy Rebello, Ibrahim Al Bakir, William J. Jusko, E Bolam, Paweł Wiczling, Annette-G Ziegler, Chantal Mathieu, Bart Keymeulen, Geoff Hale, Lucienne Chatenoud, Herman Waldmann |
| المساهمون: | Faculty of Sciences and Bioengineering Sciences, Diabetes Pathology & Therapy, Diabetes Clinic, Internal Medicine Specializations, Pathologic Biochemistry and Physiology |
| المصدر: | Journal of clinical pharmacology. 50(11) |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | CD3 Complex, medicine.medical_treatment, Diabetes Mellitus, Type 1/drug therapy, Enzyme-Linked Immunosorbent Assay, Antibodies, Monoclonal, Humanized, Antibodies, Monoclonal/administration & dosage, CD3 Complex/immunology, Double-Blind Method, Pharmacokinetics, medicine, Hypoglycemic Agents, Insulin, Humans, Pharmacology (medical), Receptor, Pharmacology, Type 1 diabetes, Dose-Response Relationship, Drug, biology, Chemistry, Antibodies, Monoclonal, Otelixizumab, Flow Cytometry, Hypoglycemic Agents/administration & dosage, medicine.disease, Diabetes Mellitus, Type 1, Cytokine, Immunology, Monoclonal, biology.protein, Antibody, Insulin/administration & dosage, surface plasmon resonance, Half-Life, medicine.drug |
| الوصف: | Otelixizumab is a chimeric CD3 antibody that has been genetically engineered to remove the glycosylation site in the Fc domain. This limits its ability to bind to complement or Fc receptors and reduces the risk of adverse clinical reactions due to cytokine release. In a trial for treatment of type 1 diabetes, a short treatment with otelixizumab resulted in a reduced requirement for insulin lasting at least 18 months. In the course of this trial, the blood concentrations of the antibody were measured by flow cytometry to determine its pharmacokinetic profile. Dose-dependent accumulation of otelixizumab was demonstrated and modeling of the data indicated that the terminal half-life was approximately 1.5 days. Antibody responses to otelixizumab were measured by 2 methods: a bridging enzyme-linked immunosorbent assay and surface plasmon resonance. The surface plasmon resonance method had a greater sensitivity and was able to detect responses in all patients, starting at 8 days after the commencement of therapy. Neutralizing antibodies were detected in a significant proportion of patients by days 22 to 29. Although no adverse clinical effects were associated with these antibody responses and they did not appear to affect the clearance of the drug, they might have important implications for possible retreatment of the patients. |
| اللغة: | English |
| تدمد: | 1552-4604 0091-2700 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2f167e311334bb702ea4be6ba8d6077Test http://ora.ox.ac.uk/objects/uuid:5f03757f-a5b6-4ae2-a737-180e856004c3Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e2f167e311334bb702ea4be6ba8d6077 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15524604 00912700 |
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