An exploratory study of the pharmacokinetics, safety, and erythropoietic effects of roxadustat in healthy cats

Hypoxia-inducible factor–prolyl hydroxylase (HIF-PH) inhibitors stimulate endogenous erythropoietin (EPO) production and are used for the treatment of anemia of chronic kidney disease (CKD) in humans. In veterinary medicine, molidustat (MOL) has demonstrated acceptable safety and efficacy with anemia of CKD in cats. Roxadustat (ROX) is another HIF-PH inhibitor that has a longer half-life than MOL, allowing for less frequent dosing. Therefore, ROX may offer an advantage in improving medication adherence. However, the safe dose range and erythropoietic effects of ROX in cats remain unclear. In the present study, an exploratory pharmacokinetic analysis of single-dose ROX administration was conducted in healthy cats to assess its safety and erythropoietic effects. In addition, a repeated-dose study was performed to evaluate safety and tolerability during continued administration. In the single-dose study, no apparent adverse events were observed at doses ≤20 mg/kg; however, severe adverse events including vomiting and systemic clinical signs leading to death were observed at 80 mg/kg, indicating that high-dose administration should be avoided. Following ROX administration, increases in reticulocyte counts and serum EPO concentrations were observed, suggesting erythropoietic activity in cats. In the repeated-dose study, ROX administered at 5–8 mg/kg for six weeks was not associated with apparent adverse events based on clinical condition and complete blood count. These results suggest that this dose range may serve as a candidate for future clinical evaluation in CKD cats.