Pharmacokinetic/pharmacodynamic modeling of roxadustat's effect on LDL cholesterol in patients in Japan with dialysis-dependent chronic kidney disease and anemia

The objective of this analysis was to develop and evaluate a pharmacokinetic/pharmacodynamic (PK/PD) model of the effect of roxadustat on low-density lipoprotein cholesterol (LDL-C) in Japanese patients with anemia of dialysis-dependent chronic kidney disease while considering the impact of covariates on model parameters. A total of 2330 LDL-C measurements from 275 patients in 3 clinical studies were analyzed using a nonlinear-mixed effects modeling approach in NONMEM software. The PK/PD relationship between roxadustat exposure and LDL-C was well described by a kinetic-pharmacodynamic model with a physiological indirect response model as the PD component. Co-administered statin usage, sevelamer usage, type of dialysis (hemodialysis or peritoneal dialysis), and sex were selected as covariates for LDLbaseline. Weight was selected as a covariate for ID50. Imax and ID50 were estimated as 0.661 and 1.51 mg/h, respectively. Roxadustat can decrease LDL-C independent of statins and sevelamer. Further study of the ability of roxadustat to lower LDL-C and any potential effects on outcomes is needed.