Pharmacokinetics, mass balance, and metabolism of [¹⁴C]SAF-189s, a potent anaplastic lymphoma kinase/c-ROS proto-oncogene 1 inhibitor in humans: Metabolism potentially affected by interaction of cytochrome P450 enzymes and intestinal microbiota.

ABSTRACT: SAF-189s is a promising highly selective, brain-penetrant, next-generation inhibitor of anaplastic lymphoma kinase (ALK) and c-ROS proto-oncogene 1 (ROS1). The pharmacokinetics, mass balance, and metabolism of SAF-189s were measured in 6 healthy Chinese male participants after receiving a single oral dose of 160 mg [¹⁴C]SAF-189s (150 μCi). SAF-189s was rapidly absorbed with a median T_max of 4.0 hours. The arithmetic mean half-life of total radioactivity in plasma was approximately 32.1 hours. The ratio of mean total drug-related substance concentration in whole blood to that in plasma (B/P_AUC) was 3.06, indicating that the drug was predominantly distributed in blood cells. After 336 hours of drug administration, the average cumulative excretion of radioacti

SUBMITTER: Yang M 

PROVIDER: S-EPMC12597534 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature