Human pharmacokinetics/pharmacodynamics of an interleukin-4 and interleukin-13 dual antagonist in asthma.

Pitrakinra, a 15-kDa recombinant human interleukin-4 mutein, targets allergic Th2 inflammation by competitively binding to interleukin-4 receptor alpha to interfere with interleukin-4 and interleukin-13 action. The authors characterized pitrakinra pharmacokinetics using data from 96 atopic patients, then compared pharmacokinetics with pharmacological response in asthma following subcutaneous versus inhalation dosing. A 1-compartment systemic model with site-specific absorption describes pitrakinra pharmacokinetics following subcutaneous, nebulization, and inhalation powder delivery. Typical CL/F and V/F, referenced to subcutaneous administration, are 15.5 L/h and 67.5 L, yielding a 3.0-hour half-life of plasma decline. Absorption into the blood (half-life