Combining "Bottom-up" and "Top-down" Approaches to Assess the Impact of Food and Gastric pH on Pictilisib (GDC-0941) Pharmacokinetics.

ABSTRACT: Pictilisib, a weakly basic compound, is an orally administered, potent, and selective pan-inhibitor of phosphatidylinositol 3-kinases for oncology indications. To investigate the significance of high-fat food and gastric pH on pictilisib pharmacokinetics (PK) and enable label recommendations, a dedicated clinical study was conducted in healthy volunteers, whereby both top-down (population PK, PopPK) and bottom-up (physiologically based PK, PBPK) approaches were applied to enhance confidence of recommendation and facilitate the clinical development through scenario simulations. The PopPK model identified food (for absorption rate constant (K_a )) and proton pump inhibitors (PPI, for relative bioavailability (F_rel ) and K_a ) as significant covariates. Food and

SUBMITTER: Lu T 

PROVIDER: S-EPMC5702897 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature