Antineoplastic agents —> Protein kinase inhibitors
Mechanism of action: Palbociclib works by blocking proteins called cyclin-dependent kinase 4 and 6, which regulate cell growth and division. Blocking these proteins can slow down growth of cancer cells and delay the progression of your cancer. Palbociclib is used to treat patients with certain types of breast cancer (hormone receptor-positive, human epidermal growth factor receptor 2-negative) which have spread beyond the original tumor and/or to other organs. It is given together with aromatase inhibitors, which are used as hormonal anticancer therapies.
Absorption: The mean Cmax of palbociclib is generally observed between 6 to 12 hours (time to reach maximum concentration, Tmax) following oral administration. The mean absolute bioavailability of Palbociclib after an oral 125 mg dose is 46%. In the dosing range of 25 mg to 225 mg, the AUC and Cmax increased proportionally with dose in general. Steady state was achieved within 8 days following repeated once daily dosing. With repeated once daily administration, palbociclib accumulated with a median accumulation ratio of 2.4 (range 1.5 to 4.2).
Distribution: Binding of palbociclib to human plasma proteins in vitro was approximately 85%, with no concentration dependence over the concentration range of 500 ng/mL to 5000 ng/mL. The geometric mean apparent volume of distribution (Vz/F) was 2583 L (26% CV).
Elimination: The geometric mean apparent oral clearance (CL/F) of palbociclib was 63.1 L/hr (29% CV), and the mean (± standard deviation) plasma elimination half-life was 29 (±5) hours in patients with advanced breast cancer. In 6 healthy male subjects given a single oral dose of [14C]palbociclib, a median of 91.6% of the total administered radioactive dose was recovered in 15 days; feces (74.1% of dose) was the major route of excretion, with 17.5% of the dose recovered in urine. The majority of the material was excreted as metabolites.