, WI *This article represents the scientific opinion of many experts and, in particular, is derived from a series of workshops held under the auspices of the Federation International Pharmaceutique (FIP) and cosponsored by the Royal Pharmaceutical Society (UK), the Bundesverband der Pharmazeutischen Industrie (BPI), Colloquium Pharmaceuticum (Germany), the American Association of Pharmaceutical Scientists (AAPS, US), and the US Food and Drug Administration. It is
Ribociclib (KISQALI), a cyclin‐dependent kinase 4/6 inhibitor approved for the first‐line treatment of HR+/HER2– advanced breast cancer with an aromatase inhibitor, is administered with no restrictions on concomitant gastric pH‐elevating agents or food intake. The influence of proton pump inhibitors (PPIs) on ribociclib bioavailability was assessed using 1) biorelevant media solubility, 2) physiologically based pharmacokinetic (PBPK) modeling, 3) noncompartmental analysis (NCA) of clinical trial data, and 4) population PK (PopPK) analysis. This multipronged approach indicated no effect of gastric pH changes on ribociclib PK and served as a platform for supporting ribociclib labeling language, stating no impact of gastric pH‐altering agents on the absorption of ribociclib, without a dedicated drug–drug interaction trial. The bioequivalence of ribociclib exposure with or without a high‐fat meal was demonstrated in a clinical trial. Lack of restrictions on ribociclib dosing may facilitate better patient compliance and therefore clinical benefit.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.