Pharmacokinetics of Nintedanib in Subjects With Hepatic Impairment
| Autor: | David Schnell, Raimund Kuelzer, Gunther Kretschmar, Claudia Dallinger, Ulrike Schmid, Kristell Marzin, Doreen Luedtke, Rozsa Schlenker-Herceg, Sandrine Kraemer |
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| Rok vydání: | 2017 |
| Předmět: |
Male
medicine.medical_specialty Indoles Cmax Pharmacology Gastroenterology 03 medical and health sciences chemistry.chemical_compound Idiopathic pulmonary fibrosis biological availability 0302 clinical medicine Pharmacokinetics Oral administration Internal medicine Medicine Humans Pharmacology (medical) Adverse effect Protein Kinase Inhibitors adverse drug event Aged medicine.diagnostic_test business.industry Liver Diseases protein‐tyrosine kinases Middle Aged medicine.disease digestive system diseases Special Populations 030228 respiratory system chemistry Tolerability 030220 oncology & carcinogenesis Nintedanib Female liver function tests business Liver function tests absorption |
| Zdroj: | Journal of Clinical Pharmacology |
| ISSN: | 1552-4604 |
| Popis: | Nintedanib is an intracellular inhibitor of tyrosine kinases used in the treatment of non–small cell lung cancer and idiopathic pulmonary fibrosis (IPF). This phase 1 open‐label study investigated the influence of mild and moderate hepatic impairment on the pharmacokinetics (PK), safety, and tolerability of nintedanib following oral administration of a single 100‐mg dose. Subjects with hepatic impairment classified as Child‐Pugh A (mild hepatic impairment) or Child‐Pugh B (moderate hepatic impairment) were eligible. The control group comprised healthy matched subjects. Primary end points were Cmax and AUC0–∞ of nintedanib. Thirty‐three subjects received nintedanib (8 in each of the Child‐Pugh A and Child‐Pugh B groups and 17 controls). The shape of the plasma concentration–time curve for nintedanib was similar between Child‐Pugh A or B and healthy subjects. Nintedanib exposure was ∼2‐fold higher in Child‐Pugh A subjects and ∼8‐fold higher in Child‐Pugh B subjects than in healthy subjects. Adverse events were reported in 3 Child‐Pugh B subjects (37.5%), no Child‐Pugh A subjects, and 3 healthy subjects (17.6%). In conclusion, exposure to nintedanib was higher in Child‐Pugh A and B subjects than in matched healthy subjects. A single dose of nintedanib 100 mg had an acceptable safety and tolerability profile in subjects with hepatic impairment. Results of this dedicated phase 1 study are in line with exploratory investigations into the PK of nintedanib in patients with advanced solid tumors or IPF and hepatic impairment. |
| Databáze: | OpenAIRE |
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