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A Mass Balance Study of14C‐Labeled JTZ‐951 (Enarodustat), a Novel Orally Available Erythropoiesis‐Stimulating Agent, in Patients With End‐Stage Renal Disease on Hemodialysis
- Source :
- Clinical Pharmacology in Drug Development. 9:728-741
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- The mass balance, pharmacokinetics, and biotransformation of JTZ-951 (enarodustat), a novel hypoxia-inducible factor prolyl hydroxylase inhibitor, were characterized in patients (N = 6) with end-stage renal disease on hemodialysis. Following a 10-mg (100 µCi) oral dose of 14 C-JTZ-951, whole blood, feces, dialysate, and, if feasible, urine were obtained for pharmacokinetic assessments and for metabolite profiling and identification in appropriate matrices. Fecal excretion was the major route of elimination of radioactivity, and urinary excretion a minor route, with mean (coefficient of variation [%CV]) recovery of 77.1 (16.2)% and 10.9 (92.0)% of the dose, respectively. Radioactivity was not detected in the dialysate, and mean (%CV) total recovery in excreta was 88.0 (14.9)%. For parent JTZ-951 in plasma, the mean (%CV) effective half-life was 8.96 (7.7)% hours, and area under the curve over 24 hours comprised the majority (>80%) of total exposure, with relatively low variability in these pharmacokinetic variables. Based on profiling of plasma radioactivity, parent JTZ-951 was the predominant circulating component, accounting for 93.7% or more of radioactivity, and metabolite M2 (hydroxylated product) was the only detectable metabolite, but its exposure was minor (
- Subjects :
- business.industry
Metabolite
medicine.medical_treatment
Area under the curve
Pharmaceutical Science
Urine
Pharmacology
030226 pharmacology & pharmacy
End stage renal disease
Excretion
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
chemistry
Pharmacokinetics
030220 oncology & carcinogenesis
Medicine
Pharmacology (medical)
Hemodialysis
business
Whole blood
Subjects
Details
- ISSN :
- 21607648 and 2160763X
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Clinical Pharmacology in Drug Development
- Accession number :
- edsair.doi...........f0083e55fecc7c89c32991b87022fd0b