Romiplostim dose response in patients with immune thrombocytopenia

J Clin Pharmacol. 2012 Oct;52(10):1540-51. doi: 10.1177/0091270011420843. Epub 2011 Dec 13.


A pharmacodynamic model was developed for platelet counts in 52 patients with immune thrombocytopenia (ITP) receiving subcutaneous romiplostim in 3 phase I/II studies (dose range, 0.2-10 µg/kg). The model consisted of a drug-sensitive progenitor cell compartment linked to a peripheral blood compartment through 4 transition compartments. The baseline platelet count, mean transit time, and kinetics of drug effect constant were 11.1 × 10(9)/L, 170 hours, and 0.6 day(-1), respectively. The ITP patients had a shorter platelet life span and lower progenitor cell production rates than healthy volunteers. Romiplostim response was described for 2 subpopulations. The romiplostim stimulatory effect in ITP patients was 351%/100 µg/wk and 12%/100 µg/wk in 68% and 32% of patients, respectively. Visual and numerical predictive checks suggested accurate prediction of platelet time course and durable response rate in ITP patients. Model-based simulations confirmed the effectiveness of dose reduction to prevent platelet counts >400 × 10(9)/L.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Models, Biological*
  • Platelet Count
  • Purpura, Thrombocytopenic, Idiopathic / blood*
  • Receptors, Fc / administration & dosage*
  • Receptors, Thrombopoietin / agonists*
  • Recombinant Fusion Proteins / administration & dosage*
  • Thrombopoietin / administration & dosage*
  • Young Adult


  • Receptors, Fc
  • Receptors, Thrombopoietin
  • Recombinant Fusion Proteins
  • Thrombopoietin
  • romiplostim