Base and Covariate Population Pharmacokinetic Analyses of Dupilumab Using Phase 3 Data.

ABSTRACT: Population pharmacokinetic base and covariate models were developed to study functional dupilumab for regulatory submissions, using data from healthy volunteers and patients with moderate-to-severe atopic dermatitis (AD) receiving intravenous or subcutaneous doses. Sixteen studies were pooled (N = 2115; 202 healthy volunteers, 1913 AD patients). The best model was a 2-compartment model with linear and Michaelis-Menten elimination and 3 transit compartments describing absorption. A stepwise approach to model building, with some parameters estimated using mostly rich data and subsequently fixed, was used to avoid adverse effects of sparse data and a steep target-mediated phase on pharmacokinetic parameters, which require rich sampling for proper estimation. Parameterization of models in term

SUBMITTER: Kovalenko P 

PROVIDER: S-EPMC7496533 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature