ArticleCPT: pharmacometrics & systems pharmacology2022
Model-informed drug development of voxelotor in sickle cell disease: Population pharmacokinetics in whole blood and plasma.
Article in CPT: pharmacometrics & systems pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The trial behind it
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Who cites it
4 citing papers in PubMed, 5 citations in OpenAlex.
- Safety, Pharmacokinetics, and Pharmacodynamics of Osivelotor for Sickle Cell Disease: First-in-Human Studies in Healthy Participants and Patients.Clinical pharmacology and therapeutics · 2026Trial
- Metabolic profile characterization of voxelotor in human urine based on in vivo and in vitro models for doping control.Analytical and bioanalytical chemistry · 2024Article
- Model-informed drug development of voxelotor in sickle cell disease: Population pharmacokinetics in whole blood and plasma.CPT: pharmacometrics & systems pharmacology · 2022Article
- Model-informed drug development of voxelotor in sickle cell disease: Exposure-response analysis to support dosing and confirm mechanism of action.CPT: pharmacometrics & systems pharmacology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxbryta (voxelotor) is a small-molecule inhibitor of sickle hemoglobin (Hb) polymerization approved for patients with sickle cell disease (SCD) aged greater than or equal to 12 years at a dose of 1500 mg once daily (q.d.). Voxelotor binds preferentially to Hb, and voxelotor partitioning into red blood cells is an effective predictor of Hb occupancy. The objectives of these analyses were to develop a population pharmacokinetic (PopPK) model for voxelotor in both plasma and whole blood in adults and adolescents to support the dose selection for optimal target engagement and to identify covariates that have a significant effect on voxelotor pharmacokinetics (PK) in plasma and whole blood. An integrated plasma and whole blood PopPK model with two compartments, first-order absorption and elimination, and a site-of-action effect compartment adequately described the concentration-time profiles of voxelotor in plasma and whole blood in patients treated up to 72 weeks. Covariates with significant effects on voxelotor PK included baseline blood volume on apparent volume of the central compartment and time-varying hematocrit and dose on whole blood partitioning, indicating that clinical markers of voxelotor effect can, in turn, influence its PK. Furthermore, the model confirmed that voxelotor PK in plasma and whole blood is linear with dose and time and comparable for adults and adolescents. No clinically important covariate effects on voxelotor PK that warranted dose adjustment were identified in this analysis. Overall, the PopPK analyses contributed significantly to the voxelotor label and support 1500 mg q.d. as the therapeutic dose in adults and adolescents with SCD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.