Effect of Moderate Hepatic Impairment on the Pharmacokinetics of Vadadustat, an Oral Hypoxia‐Inducible Factor Prolyl Hydroxylase Inhibitor

2021 ◽  
Author(s):  
Ajit Chavan ◽  
Leontia Burke ◽  
Rishikesh Sawant ◽  
Pamela Navarro‐Gonzales ◽  
Dennis Vargo ◽  
...  
Keyword(s):  
Hepatic Impairment ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Moderate Hepatic Impairment ◽  
Prolyl Hydroxylase Inhibitor

scholarly journals Effect of Moderate Hepatic Impairment on the Pharmacokinetics and Pharmacodynamics of Roxadustat, an Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor

2016 ◽  
Vol 36 (9) ◽  
pp. 743-751 ◽  
Author(s):  
Dorien Groenendaal-van de Meent ◽  
Martin den Adel ◽  
Jan Noukens ◽  
Sanne Rijnders ◽  
Axel Krebs-Brown ◽  
...  
Keyword(s):  
Hepatic Impairment ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Moderate Hepatic Impairment ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Prolyl Hydroxylase Inhibitor

scholarly journals FP390MODERATE HEPATIC IMPAIRMENT HAS ONLY A MINOR IMPACT ON THE PHARMACOKINETICS OF ROXADUSTAT, AN ORAL HYPOXIA-INDUCIBLE FACTOR PROLYL-HYDROXYLASE INHIBITOR

2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii199-iii199
Author(s):  
Dorien Groenendaal−van de Meent ◽  
Martin den Adel ◽  
Jan Noukens ◽  
Sanne Rijnders ◽  
Axel Krebs-Brown ◽  
...  
Keyword(s):  
Hepatic Impairment ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Prolyl Hydroxylase Inhibitor ◽  
A Minor

scholarly journals A Novel Hypoxia-Inducible Factor−Prolyl Hydroxylase Inhibitor (GSK1278863) for Anemia in CKD: A 28-Day, Phase 2A Randomized Trial

2016 ◽  
Vol 67 (6) ◽  
pp. 861-871 ◽  
Author(s):  
Richard A. Brigandi ◽  
Brendan Johnson ◽  
Coreen Oei ◽  
Mark Westerman ◽  
Gordana Olbina ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Prolyl Hydroxylase Inhibitor

scholarly journals Safety, Pharmacodynamics and Pharmacokinetics of the Oral Selective Hypoxia-inducible Factor Prolyl Hydroxylase Inhibitor Molidustat in Japanese Healthy Subjects

2018 ◽  
Vol WCP2018 (0) ◽  
pp. PO1-11-4
Author(s):  
Kenichi Yoshikawa ◽  
Miho Uemura ◽  
Kumi Matsuno ◽  
Shunji Matsuki ◽  
Koki Furusho ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Prolyl Hydroxylase Inhibitor

scholarly journals 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

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dorien Groenendaal-van de Meent ◽  
Virginie Kerbusch ◽  
Rudiger Kaspera ◽  
Begona Barroso-Fernandez ◽  
Piergiorgio Galletti ◽  
...  
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Severe Renal Impairment ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Least Square ◽  
Maximum Effect ◽  
Prolyl Hydroxylase Inhibitor ◽  
Stage Renal Disease ◽  
End Stage

Abstract 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 <30 mL/min/1.73 m2); end-stage renal disease (ESRD) on continuous ambulatory or automated peritoneal dialysis (CAPD/APD); or ESRD on 4-hour haemodialysis or haemodiafiltration (HD/HDF). Subjects in the normal RF, severely impaired RF, and ESRD on CAPD/APD groups received a single dose of 100-mg oral roxadustat on Day 1. A single-sequence design with two treatment periods (P1/P2) separated by a washout period was used for subjects with ESRD on HD/HDF; a single administration of 100-mg oral roxadustat occurred 2 hours after completion of a HD/HDF session (P1) and 2 hours before initiation of a HD/HDF session, 2 days after the previous session (P2). Plasma and urine PK of roxadustat and its circulating metabolites (O-glucuronide-, O-glucoside-, and sulphate of hydroxy-roxadustat) and plasma erythropoietin (EPO) were evaluated. Continuous heart rate monitoring was conducted. 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 <1%; urinary excretion and renal clearance of roxadustat and its metabolites decreased with lower baseline RF. Mean AUCinf and t1/2 for roxadustat’s circulating metabolites were higher in subjects with severely impaired RF and with ESRD on HD/HDF than in those with normal RF. Metabolite to parent ratio of AUCinf was <1% for O-glucuronide- and O-glucoside-roxadustat and <10% for sulphate of hydroxy-roxadustat. EPO baseline-corrected AUC from administration to last measurable concentration and EPO maximum effect were higher in subjects with severely impaired RF or with ESRD on HD/HDF than in those with normal RF. 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.

Hypoxia-inducible factor prolyl-hydroxylase inhibitor roxadustat (FG-4592) alleviates sepsis-induced acute lung injury

2020 ◽  
Vol 281 ◽  
pp. 103506
Author(s):  
Fu Han ◽  
Gaofeng Wu ◽  
Shichao Han ◽  
Zhenzhen Li ◽  
Yanhui Jia ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Prolyl Hydroxylase Inhibitor
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