We have located links that may give you full text access.
The effect of liver dysfunction on the pharmacokinetic disposition of belinostat and its five metabolites in patients with advanced cancers.
Cancer Chemotherapy and Pharmacology 2024 March 15
Belinostat was approved in 2014 for the treatment of relapsed or refractory peripheral T-cell lymphoma, however, there was insufficient data to recommend a dose in patients with moderate to severe hepatic impairment. The purpose of this analysis was to characterize the pharmacokinetic disposition of belinostat and its five metabolites in patients with advanced cancers and varying degrees of liver dysfunction. A population pharmacokinetic model was therefore developed to describe the parent-metabolite system. The final model was then implemented to assess the effect of liver impairment on each metabolic pathway of belinostat. It was determined that significant pharmacokinetic differences could only be demonstrated in patients with severe hepatic impairment. The final model estimated a 35%-47% reduction in metabolic clearance attributed to UGT1A1/2B7 glucuronidation, CYP2A6/3A4/2C9 metabolism, and β-oxidation. These hepatic impairment effects reduced between-subject variability by only 5%-8% for their respective parameter, with a large amount of remaining unexplained variability. With further validation, this model can be leveraged to assess the need for dose adjustments in this patient population.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app