Ocrelizumab in relapsing and primary progressive multiple sclerosis: Pharmacokinetic and pharmacodynamic analyses of OPERA I, OPERA II and ORATORIO
| العنوان: | Ocrelizumab in relapsing and primary progressive multiple sclerosis: Pharmacokinetic and pharmacodynamic analyses of OPERA I, OPERA II and ORATORIO |
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| المؤلفون: | Fabian Model, Ludwig Kappos, Stephen L. Hauser, Heidemarie Kletzl, Ekaterina Gibiansky, Andreas Günther, Claire Petry, Ann Herman, Francois Mercier, Yumi Yamamoto, Qing Wang |
| المصدر: | British Journal of Clinical Pharmacology British journal of clinical pharmacology, vol 87, iss 6 |
| بيانات النشر: | John Wiley and Sons Inc., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Phases of clinical research, Relapsing-Remitting, Neurodegenerative, 030226 pharmacology & pharmacy, Gastroenterology, 0302 clinical medicine, population analysis, Monoclonal, Medicine, Pharmacology (medical), 030212 general & internal medicine, Pharmacology & Pharmacy, Humanized, education.field_of_study, Pharmacology and Pharmaceutical Sciences, Multiple Sclerosis, Chronic Progressive, Chronic Progressive, Original Article, medicine.drug, medicine.medical_specialty, Multiple Sclerosis, pharmacokinetic-pharmacodynamic, Population, Primary Progressive Multiple Sclerosis, Antibodies, Monoclonal, Humanized, Autoimmune Disease, Antibodies, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, Pharmacokinetics, Internal medicine, pharmacokinetic–pharmacodynamic, pharmacodynamics, Humans, Immunologic Factors, In patient, education, Pharmacology, business.industry, Multiple sclerosis, neurology, pharmacokinetic–, Neurosciences, Original Articles, medicine.disease, Brain Disorders, pharmacodynamic, Pharmacodynamics, Ocrelizumab, business |
| الوصف: | AimsOcrelizumab is a humanized monoclonal antibody that selectively targets CD20-positive B cells and is indicated for treatment of patients with relapsing forms of multiple sclerosis (RMS) or primary progressive multiple sclerosis (PPMS). The pharmacokinetics and pharmacodynamics of ocrelizumab in patients with RMS or PPMS were assessed.MethodsA population pharmacokinetic model was developed based on data from the Phase II study and the Phase III studies OPERA I and OPERA II in patients with RMS. Data from the ORATORIO Phase III study in patients with PPMS became available after model finalization and was used for external model evaluation.ResultsThe ocrelizumab serum concentration vs time course was accurately described by a 2-compartment model with time-dependent clearance. Body weight was found to be the main covariate. The area under the concentration-time curve over the dosing interval was estimated to be 26% higher for patients with RMS weighing 90kg when compared with the 60-90kg group. The terminal half-life of ocrelizumab was estimated as 26days. The extent of B-cell depletion in blood, as the pharmacodynamic marker, was greater with increasing ocrelizumab exposure.ConclusionThe pharmacokinetics of ocrelizumab was described with pharmacokinetic parameters typical for an immunoglobulin G1 monoclonal antibody, with body weight as the main covariate. The pharmacokinetics and B-cell depletion in blood were comparable across the RMS and PPMS trials, and the extent of blood B-cell depletion was greater with higher exposure. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1365-2125 0306-5251 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8811580eb5543d689634ed86d7b68a05Test http://europepmc.org/articles/PMC8247316Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8811580eb5543d689634ed86d7b68a05 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13652125 03065251 |
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