abt-199 and Hepatic-Insufficiency

Venetoclax is a selective B cell lymphoma-2 inhibitor. It is approved for treatment of chronic lymphocytic leukemia and is being investigated for other hematological malignancies. Venetoclax is predominantly eliminated by the liver; therefore, there is a need to investigate the effect of hepatic insufficiency on venetoclax pharmacokinetics.. A phase I study was carried out in 24 women with normal hepatic function or mild, moderate, or severe hepatic impairment (based on Child-Pugh scores), who received a single 50 mg dose of venetoclax with a low-fat meal. Blood samples were collected up to 120 h after venetoclax administration. Pharmacokinetic parameters were estimated using non-compartmental methods.. Venetoclax maximum observed plasma concentration (C. No venetoclax dosage adjustment is required in subjects with mild or moderate hepatic impairment. In subjects with severe hepatic impairment, a 50% dose reduction of venetoclax is recommended to account for higher exposures and the longer half-life.

Topics: Administration, Oral; Aged; Antineoplastic Agents; Bridged Bicyclo Compounds, Heterocyclic; Case-Control Studies; Female; Half-Life; Hepatic Insufficiency; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Safety; Sulfonamides