The Effect of a High‐Fat Meal on the Pharmacokinetics of Brigatinib, an Oral Anaplastic Lymphoma Kinase Inhibitor, in Healthy Volunteers
| Autor: | Michael J. Hanley, Meera Tugnait, Karthik Venkatakrishnan, David Kerstein, Daryl Sonnichsen, Narayana I. Narasimhan, David J. Dorer, Neeraj Gupta |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male brigatinib medicine.medical_specialty Brigatinib non–small‐cell lung cancer Population Administration Oral Biological Availability Pharmaceutical Science Original Manuscript Diet High-Fat 030226 pharmacology & pharmacy Gastroenterology Absorption Food-Drug Interactions Young Adult 03 medical and health sciences Organophosphorus Compounds 0302 clinical medicine Pharmacokinetics Internal medicine food effect Humans Anaplastic lymphoma kinase Medicine Pharmacology (medical) education Adverse effect Protein Kinase Inhibitors Ontario Meal education.field_of_study Cross-Over Studies Crizotinib business.industry Articles Fasting anaplastic lymphoma kinase Crossover study Healthy Volunteers Pyrimidines 030220 oncology & carcinogenesis Female business Tablets medicine.drug |
| Zdroj: | Clinical Pharmacology in Drug Development |
| ISSN: | 2160-7648 2160-763X |
| DOI: | 10.1002/cpdd.641 |
| Popis: | Brigatinib, a next‐generation anaplastic lymphoma kinase (ALK) inhibitor, received accelerated approval in the United States for the treatment of patients with metastatic ALK+ non–small‐cell lung cancer who have progressed on or are intolerant to crizotinib. A clinical study was conducted to assess the effect of food on brigatinib pharmacokinetics (PK). Healthy subjects received a single oral dose of brigatinib 180 mg (2 × 90‐mg tablets) after a 10‐hour fast or after a high‐fat meal in a 2‐period, 2‐sequence crossover study. Plasma samples for PK characterization were collected over 168 hours postdose. Twenty‐four subjects were enrolled (mean age 44 years; 58% male), with 21 included in the PK‐evaluable population. Brigatinib peak concentration was reduced by 13% under fed (high‐fat meal) versus fasted conditions, with no effect on area under the concentration‐time curve. The median time to peak concentration of brigatinib was longer under fed conditions (5 hours) than in fasted conditions (2 hours). Treatment‐emergent adverse events were similar under fasted (48%) and fed (46%) conditions and were of mild intensity. Consumption of a high‐fat meal decreased the rate of brigatinib oral absorption but had no impact on the extent of absorption, thereby supporting brigatinib administration without regard to meals. These recommendations are reflected in the US prescribing information for brigatinib. |
| Databáze: | OpenAIRE |
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