Population Pharmacokinetics of Palbociclib in aReal-World Situation.
Fiche publication
Date publication
février 2021
Journal
Pharmaceuticals (Basel, Switzerland)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LADOIRE Sylvain, Dr ROYER Bernard, Dr DESMOULINS Isabelle, Pr SCHMITT Antonin, Dr FUMET Jean-David, Dr HENNEQUIN Audrey, Dr MAYEUR Didier
Tous les auteurs :
Royer B, Kaderbhaï C, Fumet JD, Hennequin A, Desmoulins I, Ladoire S, Ayati S, Mayeur D, Ilie S, Schmitt A
Lien Pubmed
Résumé
Palbociclib is an oral cyclin-dependent kinase inhibitor that is used in combination with aromatase inhibitors in the treatment of postmenopausal women with metastatic breast cancer. Its metabolism profile is associated with an important interpatient variability. We performed a population pharmacokinetics study of palbociclib in women routinely followed in a cancer center. One hundred and fifty-one samples were analyzed. The sampling times after administration ranged from 0.9 to 75 h and the samples were taken between 1 and 21 days after the beginning of the palbociclib cycle. Palbociclib was determined using a validated mass spectrometry method. The best model that described the concentrations was a one-compartment model with first-order absorption and an absorption lag time. Interindividual variability could only be estimated on the clearance and the first-order absorption. Creatinine clearance was found to be a significant covariate for the apparent clearance. No significant covariates could be observed with the first-order absorption. First-order absorption and absorption lag times were difficult to assess because of the constraints linked to the real-world setting due to the small number of samples used during the absorption process. However, palbociclib apparent clearance was satisfactorily estimated. Population pharmacokinetics (POP PK) with palbociclib could help to optimize dosing.
Mots clés
palbociclib, population pharmacokinetics, real-world situation
Référence
Pharmaceuticals (Basel). 2021 Feb 24;14(3):