التفاصيل البيبلوغرافية
| العنوان: |
Population pharmacokinetic model with time‐varying clearance for lorlatinib using pooled data from patients with non‐small cell lung cancer and healthy participants |
| المؤلفون: |
Chen, Joseph, Houk, Brett, Pithavala, Yazdi K., Ruiz‐Garcia, Ana |
| المساهمون: |
Pfizer |
| المصدر: |
CPT: Pharmacometrics & Systems Pharmacology ; volume 10, issue 2, page 148-160 ; ISSN 2163-8306 2163-8306 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2021 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
Lorlatinib, a selective inhibitor of anaplastic lymphoma kinase (ALK) and c‐ROS oncogene 1 (ROS1) tyrosine kinase, is indicated for the treatment of ALK‐positive metastatic non‐small cell lung cancer (NSCLC) following progression on crizotinib and at least one other ALK inhibitor, or alectinib/ceritinib as the first ALK inhibitor therapy for metastatic disease. The population pharmacokinetics (PopPK) of lorlatinib was conducted by nonlinear mixed effects modeling of data from 330 patients with ALK‐positive or ROS1‐positive NSCLC and 95 healthy participants from six phase I studies in healthy volunteers; demographic, metabolizer phenotype, and patient prognostic factors were evaluated as covariates. Lorlatinib plasma PK was well‐characterized by a two‐compartment model with sequential zero‐order and first‐order absorption and a time‐varying induction of clearance. Single dose clearance was estimated to be 9.04 L/h. Assuming that the metabolic auto‐induction of lorlatinib reaches saturation in ~ 5 half‐lives, clearance was estimated to approach a maximum of 14.5 L/h at steady‐state after a period of ~ 7.25 days. The volume of distribution of the central compartment was estimated to be 121 L and the first‐order absorption rate constant was estimated to be 3.1 h −1 . Baseline albumin and lorlatinib total daily dose were significant covariates on lorlatinib clearance. Use of proton pump inhibitors was found to be a significant covariate on the lorlatinib absorption rate constant. These factors were assessed to have no clinically meaningful impact on lorlatinib plasma exposure, and no dose adjustments are considered necessary based on the examined covariates. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1002/psp4.12585 |
| الإتاحة: |
https://doi.org/10.1002/psp4.12585Test |
| حقوق: |
http://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: |
edsbas.18E12F2F |
| قاعدة البيانات: |
BASE |
