دورية أكاديمية
Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC
| العنوان: | Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC |
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| المؤلفون: | Agustos Cetin Ozbey, David Combarel, Vianney Poinsignon, Christine Lovera, Esma Saada, Olivier Mir, Angelo Paci |
| المصدر: | Pharmaceuticals, Vol 14, Iss 9, p 927 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine LCC:Pharmacy and materia medica |
| مصطلحات موضوعية: | cancer, tyrosine kinase inhibitors, population pharmacokinetics, therapeutic drug monitoring (TDM), Medicine, Pharmacy and materia medica, RS1-441 |
| الوصف: | Pazopanib is a potent multi-targeted kinase inhibitor approved for the treatment of advanced renal cell carcinoma and soft tissue sarcoma. The pharmacokinetics of pazopanib is characterized by a significant inter- and intra-patient variability and a target through plasma concentration of 20.5 mg·L−1. However, routine monitoring of trough plasma concentrations at fixed hours is difficult in daily practice. Herein, we aimed to characterize the pharmacokinetic (PK) profile of pazopanib and to identify a target area under the curve (AUC) more easily extrapolated from blood samples obtained at various timings after drug intake. A population pharmacokinetic (popPK) model was constructed to analyze pazopanib PK and to estimate the pazopanib clearance of a patient regardless of the time of sampling. Data from the therapeutic drug monitoring (TDM) of patients with cancer at Institute Gustave Roussy and a clinical study (phase I/II) that evaluates the tolerance to pazopanib were used. From the individual clearance, it is then possible to obtain the patient’s AUC. A target AUC for maximum efficacy and minimum side effects of 750 mg·h·L−1 was determined. The comparison of the estimated AUC with the target AUC would enable us to determine whether plasma exposure is adequate or whether it would be necessary to propose therapeutic adjustments. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1424-8247 |
| Relation: | https://www.mdpi.com/1424-8247/14/9/927; https://doaj.org/toc/1424-8247 |
| DOI: | 10.3390/ph14090927 |
| URL الوصول: | https://doaj.org/article/e8cfeab0bde14f9aa7e0028b6aa6411d |
| رقم الأكسشن: | edsdoj.8cfeab0bde14f9aa7e0028b6aa6411d |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14248247 |
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| DOI: | 10.3390/ph14090927 |