دورية أكاديمية
Population Pharmacokinetics of the Anti-Interferon-Gamma Monoclonal Antibody Emapalumab: An Updated Analysis
| العنوان: | Population Pharmacokinetics of the Anti-Interferon-Gamma Monoclonal Antibody Emapalumab: An Updated Analysis |
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| المؤلفون: | Patrick Brossard, Christian Laveille |
| المصدر: | Rheumatology and Therapy, Vol 11, Iss 3, Pp 869-880 (2024) |
| بيانات النشر: | Adis, Springer Healthcare, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Diseases of the musculoskeletal system |
| مصطلحات موضوعية: | Adult-onset Still’s disease, Emapalumab, Hemophagocytic lymphohistiocytosis, Hyperinflammation, Interferon-gamma, Modeling, Diseases of the musculoskeletal system, RC925-935 |
| الوصف: | Abstract Introduction Emapalumab is a fully human monoclonal antibody that targets free and receptor-bound interferon-gamma (IFNγ), neutralizing its biological activity. IFNγ levels differ by orders of magnitude between patients with primary hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS; a form of secondary HLH) in systemic juvenile idiopathic arthritis (sJIA). Therefore, this study aimed to develop a population pharmacokinetic model for emapalumab across a patient population with a wide range of total (free and emapalumab-bound) IFNγ levels using observations from patients with primary HLH or MAS in sJIA in clinical trials. Methods Pharmacokinetic data were pooled (n = 58; 2709 observations) from studies enrolling patients administered emapalumab for primary HLH or MAS in sJIA. Patients with primary HLH were administered emapalumab 1 mg/kg (potentially increasing to 3, 6, and up to 10 mg/kg based on clinical response) every 3 days. Patients with MAS in sJIA were administered emapalumab 6 mg/kg, followed by 3 mg/kg every 3 days until day 15 and twice weekly until day 28. An earlier population PK model was re-parameterized using this data. Results The final model for emapalumab comprised a 2-compartment model with first-order elimination. Emapalumab clearance remains constant when the total IFNγ concentration (free and emapalumab-bound) is |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2198-6576 2198-6584 |
| العلاقة: | https://doaj.org/toc/2198-6576Test; https://doaj.org/toc/2198-6584Test |
| DOI: | 10.1007/s40744-024-00669-y |
| الوصول الحر: | https://doaj.org/article/3269a63113544c5fb3eb1d9820a75c89Test |
| رقم الانضمام: | edsdoj.3269a63113544c5fb3eb1d9820a75c89 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 21986576 21986584 |
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| DOI: | 10.1007/s40744-024-00669-y |