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Pharmacokinetics, Pharmacodynamics, and Tolerability of Concomitant Administration of Verinurad and Febuxostat in Healthy Male Volunteers
- Source :
- Clinical Pharmacology in Drug Development
- Publication Year :
- 2017
-
Abstract
- Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in development for treatment of gout and asymptomatic hyperuricemia. This phase 1, single‐blind, multiple‐dose, drug‐drug interaction study evaluated the pharmacokinetics (PK), pharmacodynamics, and safety/tolerability of verinurad in combination with febuxostat in healthy male volunteers. Twenty‐three subjects were randomized and received once‐daily doses of verinurad (or placebo) or febuxostat alone (days 1‐7 and days 15‐21), or verinurad + febuxostat on days 8‐14. For combinations, subjects received verinurad 10 mg + febuxostat 40 mg or verinurad 2.5 mg + febuxostat 80 mg. Plasma/serum and urine samples were analyzed for verinurad, febuxostat, and uric acid. Safety was assessed by adverse events and laboratory tests. Febuxostat 40 mg had no effect on plasma exposure of verinurad 10 mg, whereas febuxostat 80 mg increased the maximum observed plasma concentration and the area under the plasma concentration‐time curve of verinurad 2.5 mg by 25% and 33%, respectively. Verinurad had no effect on febuxostat PK. Maximal reduction in serum urate was 76% with verinurad 10 mg + febuxostat 40 mg versus verinurad 10 mg (56%) or febuxostat 40 mg (49%) alone and was 67% with verinurad 2.5 mg + febuxostat 80 mg versus verinurad 2.5 mg (38%) or febuxostat 80 mg (57%) alone. Verinurad increased, whereas febuxostat decreased, 24‐hour fractional excretion and renal clearance of uric acid. There was no clinically significant drug‐drug interaction between verinurad and febuxostat PK. The combination resulted in greater reductions of serum urate than either drug alone and was well tolerated at the studied doses.
- Subjects :
- Adult
Male
Pyridines
Pharmaceutical Science
Original Manuscript
Pharmacology
Naphthalenes
030226 pharmacology & pharmacy
Drug Administration Schedule
Excretion
03 medical and health sciences
chemistry.chemical_compound
Young Adult
0302 clinical medicine
gout
verinurad
Pharmacokinetics
medicine
pharmacodynamics
Humans
Pharmacology (medical)
Drug Interactions
Single-Blind Method
Hyperuricemia
business.industry
febuxostat
Articles
Middle Aged
medicine.disease
Healthy Volunteers
Gout
Uric Acid
Renal Elimination
Tolerability
chemistry
030220 oncology & carcinogenesis
Pharmacodynamics
Area Under Curve
Uric acid
Drug Therapy, Combination
Febuxostat
Propionates
business
pharmacokinetics
medicine.drug
Subjects
Details
- ISSN :
- 21607648
- Volume :
- 8
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Clinical pharmacology in drug development
- Accession number :
- edsair.doi.dedup.....68d5ecd6a6997541b1b5929006b0ec8f