التفاصيل البيبلوغرافية
| العنوان: |
Evaluation of the absolute oral bioavailability of the anaplastic lymphoma kinase/c-ROS oncogene 1 kinase inhibitor lorlatinib in healthy participants |
| المؤلفون: |
Hibma, Jennifer E., O’Gorman, Melissa, Nepal, Sunil, Pawlak, Sylvester, Ginman, Katherine, Pithavala, Yazdi K. |
| المصدر: |
Cancer Chemotherapy and Pharmacology ; volume 89, issue 1, page 71-81 ; ISSN 0344-5704 1432-0843 |
| بيانات النشر: |
Springer Science and Business Media LLC |
| سنة النشر: |
2021 |
| مصطلحات موضوعية: |
Pharmacology (medical), Cancer Research, Pharmacology, Toxicology, Oncology |
| الوصف: |
Purpose Lorlatinib is a third-generation tyrosine kinase inhibitor currently approved for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer. This open-label, phase 1, randomized two-sequence, two-treatment, two-period, crossover study investigated the absolute oral bioavailability of lorlatinib in healthy participants. Methods Eligible participants were randomized to receive two treatments in one of two sequences: lorlatinib 100 mg single oral dose followed by lorlatinib 50 mg intravenous (IV) dose, or lorlatinib IV dose followed by lorlatinib oral dose, each with at least a 10-day washout between successive lorlatinib doses. Blood samples for pharmacokinetics were collected for up to 144 hours (h) after dosing. Validated liquid chromatographic-tandem mass spectrometry was used to determine plasma concentrations of lorlatinib and its benzoic acid metabolite PF-06895751. Results In total, 11 participants were enrolled (mean age 37.6 years, all male). The adjusted geometric mean (90% confidence interval) for the absolute oral bioavailability was 80.78% (75.73–86.16%). Using non-compartmental analysis, the estimated arithmetic mean elimination plasma half-life of lorlatinib was 25.5 and 27.0 h after the oral and IV doses, respectively. No deaths, serious adverse events (AEs), or severe AEs were reported, and most treatment-emergent AEs were mild in severity, with two events of transaminase increase of moderate severity. All treatment-emergent AEs were resolved by the end of the study. Conclusion Both oral and IV lorlatinib were well-tolerated in healthy participants and oral lorlatinib is highly bioavailable after oral administration. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1007/s00280-021-04368-1 |
| DOI: |
10.1007/s00280-021-04368-1.pdf |
| DOI: |
10.1007/s00280-021-04368-1/fulltext.html |
| الإتاحة: |
https://doi.org/10.1007/s00280-021-04368-1Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: |
edsbas.6EC78FD5 |
| قاعدة البيانات: |
BASE |
