Pharmacodynamic effects of molidustat on erythropoiesis in healthy cats

Abstract

Background: Inhibition of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) stimulates erythropoiesis in rats, dogs, monkeys, and humans. Hypothesis/Objective: Determine if molidustat, a novel HIF-PH inhibitor, stimulates erythropoiesis in healthy cats. Animals: Seventeen healthy adult laboratory cats. Methods: Randomized, placebo-controlled study. Cats were treated PO once daily with suspensions of 0 (Group 1; n = 6), 5 (Group 2; n = 6), or 10 (Group 3; n = 5) mg/kg of molidustat. Effects on red blood cell parameters, reticulocyte indices and plasma erythropoietin (EPO) concentrations were evaluated. Molidustat treatment was stopped when hematocrit (HCT) exceeded 60%. Results: Compared to placebo, a significant increase in mean HCT was evident starting on Day 14 (Group 2:54.4% vs 40.3%, P