التفاصيل البيبلوغرافية
| العنوان: |
Phase 1 Study Evaluating the Effects of the Proton Pump Inhibitor Rabeprazole and Food on the Pharmacokinetics of Lorlatinib in Healthy Participants. |
| المؤلفون: |
Xu, Huiping, O'Gorman, Melissa T., Nepal, Sunil, James, Lee P., Ginman, Katherine, Pithavala, Yazdi K. |
| المصدر: |
Clinical Pharmacology in Drug Development; Nov2021, Vol. 10 Issue 11, p1395-1404, 10p |
| مصطلحات موضوعية: |
BIOAVAILABILITY, PROTON pump inhibitors, PHARMACOKINETICS, NON-small-cell lung carcinoma, ADVERSE health care events, MEALS, GASTRIC acid |
| مستخلص: |
Lorlatinib is approved worldwide as treatment for anaplastic lymphoma kinase‐positive and c‐ros oncogene 1‐positive non‐small cell lung cancer. The objectives of this phase 1, open‐label crossover study (NCT02569554) in healthy adult participants were to determine (1) the effects of the proton pump inhibitor (PPI) rabeprazole on lorlatinib pharmacokinetics (PK), (2) the effects of a high‐fat meal on lorlatinib PK, and (3) the relative bioavailability of an oral solution to tablet formulation of lorlatinib under fasted conditions. Participants were followed on‐study for ≥50 days after the first dose of lorlatinib. Participants received treatments over 4 periods, with a washout of ≥10 days between consecutive lorlatinib doses. Twenty‐seven participants were enrolled and received lorlatinib, and all were assessed for PK and safety. Results showed no effect of multiple doses of rabeprazole on the total plasma exposure of a single oral dose of lorlatinib 100‐mg tablets. The results also indicated that a high‐fat meal had no effect on lorlatinib PK after a single 100‐mg oral dose. In addition, the relative bioavailability of lorlatinib oral solution compared with lorlatinib tablets was complete (approximately 108%). The safety profile of lorlatinib was consistent with that reported in previous studies, and most treatment‐related adverse events were mild to moderate. These data indicate that lorlatinib can be administered with drugs that modify gastric acid, including PPIs, without restriction. These results also confirm that lorlatinib can be administered regardless of food intake. [ABSTRACT FROM AUTHOR] |
|
Copyright of Clinical Pharmacology in Drug Development is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
