Integrated Two-Analyte Population Pharmacokinetic Model of Polatuzumab Vedotin in Patients With Non-Hodgkin Lymphoma.

ABSTRACT: A two-analyte integrated population pharmacokinetic (PK) model that simultaneously describes concentrations of antibody-conjugated monomethyl auristatin E (acMMAE) and unconjugated MMAE following repeated administrations of polatuzumab vedotin (pola) was developed based on data from four clinical studies of pola in patients with non-Hodgkin lymphoma. A two-compartment model with a nonspecific, time-dependent linear clearance, a linear time-dependent exponentially declining clearance, and a Michaelis-Menten clearance provided a good fit of the acMMAE plasma PK profiles. All three acMMAE elimination pathways contributed to the input to the central compartment of unconjugated MMAE, which was also described by a two-compartment model. Population PK parameters, covariate effects, and interindiv

SUBMITTER: Lu D 

PROVIDER: S-EPMC6966185 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature