SO052EFFECT OF SEVERE RENAL IMPAIRMENT OR END-STAGE RENAL DISEASE ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF ROXADUSTAT, AN ORAL HYPOXIA-INDUCIBLE FACTOR PROLYL HYDROXYLASE INHIBITOR

Autor:	Rudiger Kaspera, Martin den Adel, Gernot K Klein, Virginie Kerbusch, Begona Barroso-Fernandez, Piergiorgio Galletti, Dorien Groenendaal-van de Meent
Rok vydání:	2020
Předmět:	Transplantation business.industry medicine.medical_treatment Renal function Pharmacology Hypoxia (medical) End stage renal disease Hypoxia-inducible factors Pharmacokinetics Nephrology Pharmacodynamics medicine Procollagen-proline dioxygenase Hemodialysis medicine.symptom business
Zdroj:	Nephrology Dialysis Transplantation. 35
ISSN:	1460-2385 0931-0509
DOI:	10.1093/ndt/gfaa139.so052
Popis:	Background and Aims Roxadustat is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor used at titrated doses to treat anaemia in CKD patients. This study investigated the pharmacokinetics (PK), metabolic profile, pharmacodynamics, and safety of roxadustat in subjects with different degrees of renal function (RF). Method This was a phase 1, open-label study conducted in Germany and the United Kingdom (EudraCT Number: 2015-002565-28). Subjects were enrolled in four RF groups: normal RF (eGFR ≥90 mL/min/1.73 m2); severely impaired RF (not on dialysis; eGFR Results Of 73 screened subjects, 34 (46.6%) were enrolled and received roxadustat (normal RF, n=12; severely impaired RF, n=9; ESRD on CAPD, n=1; ESRD on HD/HDF, n=12). The geometric least-square mean ratio of area under the plasma concentration-time curve (AUC) from administration to infinity (AUCinf) relative to subjects with normal RF was 223% (90% CI: 185, 268) and 195% (90% CI: 165, 229) in subjects with severely impaired RF and in those with ESRD on HD/HDF, respectively. Roxadustat’s maximum concentration (Cmax) and terminal elimination half-life (t1/2) were comparable between groups. The PK of roxadustat and its metabolites were not affected by HD/HDF. In subjects with normal RF, the amount of roxadustat excreted unchanged in urine was Conclusion The AUC for roxadustat and its metabolites was higher in patients with severely impaired RF or with ESRD on HD/HDF than in those with normal RF. Roxadustat’s Cmax and t1/2 were comparable among all groups. Roxadustat and its metabolites were not significantly cleared by HD/HDF.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::c07db61cb29bde5448aa021d5cd1abde https://doi.org/10.1093/ndt/gfaa139.so052 Zobrazit plný text záznamu