The summary of neratinib PK paramet

The summary of neratinib PK parameters and statistical comparison (pair-wise comparison of Child-Pugh A, B, and C to healthy subjects) are described in Table 5. Neratinib exposure levels in the Child-Pugh Class A (mild impaired) and B (moderate impaired) patients were similar to that in normal healthy volunteers. Exposure to neratinib (AUC) was increased by approximately 2.8- fold in patients with severe hepatic impairment (Child-Pugh Class C). Based on the relative contributions of the pharmacological activities to HER2 inhibition for parent compound and each active metabolites M3, M6, and M7, the combined exposure (molar concentration based active AUCs) for neratinib and active metabolites are estimated to be 2.4-fold higher in subjects with severe hepatic impairments when compared to normal hepatic functions. Given the high variability of the observed PK and pan-tyrosine kinases inhibition of neratinib, it is recommended to reduce the starting dose of neratinib to 80 mg for patients with severe hepatic impairment.