Population pharmacokinetic analysis of dupilumab in adult and adolescent patients with asthma

Abstract

A population pharmacokinetic model was developed using data from healthy subjects and patients with moderate-to-severe asthma receiving intravenous or subcutaneous dupilumab doses. A total of nine phase I to phase III studies were pooled (202 healthy subjects and 1912 patients with asthma including 68 adolescents) in the model development. The best model was a two-compartment model with parallel linear and nonlinear Michaelis-Menten elimination with first order absorption. The PK parameter estimates were distribution volume of central compartment 2.76 L, linear elimination rate 0.0418 1/day, and subcutaneous bioavailability 60.9%. Pharmacokinetics (PK) properties of dupilumab in patients with asthma were determined to be comparable to those of healthy subjects and patients with atopic dermatitis. Only body weight exerts a notable effect explaining between-subject variability in dupilumab PK, but dose adjustment for weight is not warranted based on results from clinical studies. There is no PK difference between adolescent and adult patients with asthma after correction for body weight.