Romiplostim dose–response in patients with myelodysplastic syndromes

摘要: Aim To characterize the romiplostim dose–response in subjects with low or intermediate-1 risk myelodysplastic syndromes (MDS) receiving subcutaneous romiplostim. Methods Data from 44 MDS (dose range 300–1500 μg week−1) were used to develop a pharmacodynamic model consisting of romiplostim-sensitive progenitor cell compartment linked peripheral blood through four transit compartments representing maturation bone marrow megakaryocytes platelets. A kinetics drug effect was quantify stimulatory on proliferation sensitive cells and pharmacodynamics-mediated disposition modelled by assuming constant (kDE) be proportional change platelet count relative baseline. Results The estimated values (between subject variability) for baseline count, mean time, kDE 24 × 109 l−1 (47%), 9.6 days (44%) 0.28 days−1, respectively. had shorter lifespan (42 h) than healthy (257 h). Romiplostim described responders (78%) non-responders (22%). The average weekly production rate at 269% per 100 μg week−1 responders. Body weight, age, gender race not statistically related parameters. Visual predictive checks confirmed adequacy. Conclusion The time course counts administration escalating doses characterized showed linear increase counts.