Physiologically Based Pharmacokinetic Model of Brigatinib in Healthy Volunteers and Patients With Cancer.

Brigatinib, an oral ALK inhibitor for metastatic NSCLC, lacks dosing guidance for special populations such as the Chinese. This study developed a physiologically based pharmacokinetic (PBPK) model using European data from patients with hepatic/renal impairment and drug-drug interaction (DDI) studies (itraconazole, rifampin). The model was then applied to predict (1) pharmacokinetics (PK) in the Chinese population; (2) PK in Chinese patients with hepatic/renal impairment; and (3) DDI in Chinese patients. Validated against clinical data, the model successfully predicted brigatinib PK alone and with CYP3A4 modulators. Food simulations showed a slight absorption delay without clinically meaningful exposure reduction. In hepatic/renal impairment, the model accurately predicted exposure changes across severity groups (fold error < 2). Extending the European-validated model to Chinese populations, the findings demonstrate reliable predictions of brigatinib PK in Chinese individuals as well as in Chinese patients with hepatic or renal impairment.