Metabolism, excretion and pharmacokinetics of [14C]crizotinib following oral administration to healthy subjects

Abstract1. Crizotinib (XALKORI®), an oral inhibitor of anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition factor kinase (c-Met), is currently approved for the treatment of patients with non-small cell lung cancer that is ALK-positive.2. The metabolism, excretion and pharmacokinetics of crizotinib were investigated following administration of a single oral dose of 250 mg/100 µCi [14C]crizotinib to six healthy male subjects.3. Mean recovery of [14C]crizotinib-related radioactivity in excreta samples was 85% of the dose (63% in feces and 22% in urine).4. Crizotinib and its metabolite, crizotinib lactam, were the major components circulating in plasma, accounting for 33% and 10%, respectively, of the 0–96 h plasma radioactivity. Unchanged crizotinib was the major excreted component in feces (∼53% of the dose). In urine, crizotinib and O-desalkyl crizotinib lactam accounted for ∼2% and 5% of the dose, respectively. Collectively, these data indicate that the primary clearance pathway for cri...