A semi-mechanistic population pharmacokinetic-pharmacodynamic model to assess downstream drug-target effects on erythropoiesis.

ABSTRACT: Erythropoiesis is a complex process that results in the production of erythrocytes from hematopoietic stem cells in the bone marrow. This work aimed to develop a population pharmacokinetic-pharmacodynamic (PKPD) model describing erythropoiesis and hemoglobin synthesis following bitopertin, an inhibitor of glycine transporter 1 (GlyT1), administration. Data from a Phase 1 clinical trial in 67 healthy subjects administered bitopertin (10, 30, or 60 mg) or placebo for 120 days were analyzed. Hematological assessments included erythrocyte and reticulocyte counts, immature reticulocyte fraction, hemoglobin concentration, and mean corpuscular hemoglobin. The proposed semi-mechanistic model, which leverages data and physiological knowledge, was found to adequately simultaneously describe the dose

SUBMITTER: Rognas SV 

PROVIDER: S-EPMC12289712 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature