pexidartinib and Body-Weight

Pexidartinib is a kinase inhibitor that induces tumor response and improvements in symptoms and functional outcomes in adult patients with symptomatic tenosynovial giant cell tumor (TGCT). A population pharmacokinetic (PK) model for pexidartinib and its metabolite, ZAAD, was developed, and effects of demographic and clinical factors on the PK of pexidartinib and ZAAD were estimated. The analysis included pooled data from 7 studies in healthy volunteers (N = 159) and 2 studies in patients with TGCT or other solid tumors (N = 216). A structural 2-compartment model with sequential zero- and first-order absorption and lag time, and linear elimination from the central compartment adequately described pexidartinib and ZAAD PKs. Clearance of pexidartinib was estimated at 5.83 L/h in a typical patient with reference covariates (male, non-Asian, weight = 80 kg, creatinine clearance ≥90 mL/min, aspartate aminotransferase ≤80 U/L, and total bilirubin ≤20.5 μmol/L). In the covariate analysis, Asians and healthy subjects had modestly lower pexidartinib exposure (21% decrease each) in terms of steady-state area under the curve values from 0 to 24 hours (AUC

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Aminopyridines; Antineoplastic Agents; Area Under Curve; Asian People; Bacterial Proteins; Body Weight; Creatinine; Female; Giant Cell Tumor of Tendon Sheath; Humans; Kidney Function Tests; Liver Function Tests; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Pyrroles; Racial Groups; Sex Factors; Sociodemographic Factors; Tumor Burden; Young Adult