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Pharmacokinetics of Voxelotor in Patients With Renal and Hepatic Impairment.
- Source :
-
Journal of clinical pharmacology [J Clin Pharmacol] 2021 Apr; Vol. 61 (4), pp. 493-505. Date of Electronic Publication: 2020 Oct 20. - Publication Year :
- 2021
-
Abstract
- Two open-label studies assessed the safety, tolerability, and pharmacokinetics of Oxbryta (voxelotor) in subjects with hepatic or renal impairment. Eight subjects with severe renal impairment (estimated glomerular filtration rate <30 mL/min/1.73 m <superscript>2</superscript> ) and 8 healthy age-, sex-, and body mass index-matched controls were administered a single oral dose of voxelotor 900 mg. Seven patients with mild (Child-Pugh A), moderate (Child-Pugh B), and severe (Child-Pugh C) hepatic impairment and healthy age-, sex-, and body mass index-matched controls (7:7:7:7) were administered a single oral dose of voxelotor 1500 mg, except those with severe hepatic impairment (600 mg). There was no apparent effect of renal function on the excretion of voxelotor based on comparable half-life values between subjects with severe renal impairment and healthy matched controls. Mean area under the concentration-time curve from time 0 to infinity (AUC <subscript>0-inf</subscript> ) values were lower by approximately 50% (plasma) and 25% (whole blood) in subjects with severe renal impairment compared with controls. Accordingly, dose adjustment is not required in patients with severe renal impairment. Voxelotor plasma and whole-blood exposures were slightly increased in subjects with mild and moderate hepatic impairment. Mean AUC <subscript>0-inf</subscript> values were approximately 9% to 18% higher compared with those of healthy matched controls. Dose adjustment is therefore not required in patients with mild or moderate hepatic impairment. Voxelotor mean AUC <subscript>0-inf</subscript> values were approximately 90% higher in subjects with severe hepatic impairment. A lower voxelotor dose (1000 mg) is recommended for patients with severe hepatic impairment. Voxelotor was well tolerated in all treatment groups.<br /> (© 2020 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)
- Subjects :
- Adult
Aged
Area Under Curve
Body Mass Index
Dose-Response Relationship, Drug
Female
Glomerular Filtration Rate
Half-Life
Humans
Male
Middle Aged
Benzaldehydes pharmacokinetics
Hematologic Agents pharmacokinetics
Hepatic Insufficiency metabolism
Pyrazines pharmacokinetics
Pyrazoles pharmacokinetics
Renal Insufficiency metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4604
- Volume :
- 61
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 33084052
- Full Text :
- https://doi.org/10.1002/jcph.1757