Cargando…
Population Pharmacokinetic Analysis of Rivipansel in Healthy Subjects and Subjects with Sickle Cell Disease
BACKGROUND: Sickle cell disease is an inherited blood disorder with reduced blood-carrying capacity. It is associated with a tendency to form microclots in blood vessels, leading to painful episodes known as a vaso-occlusive crisis. Rivipansel is a pan-selectin inhibitor being studied for the treatm...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206303/ https://www.ncbi.nlm.nih.gov/pubmed/33993463 http://dx.doi.org/10.1007/s40268-021-00346-3 |
_version_ | 1783708610235203584 |
---|---|
author | Nayak, Satyaprakash Tammara, Brinda Harnisch, Lutz O. |
author_facet | Nayak, Satyaprakash Tammara, Brinda Harnisch, Lutz O. |
author_sort | Nayak, Satyaprakash |
collection | PubMed |
description | BACKGROUND: Sickle cell disease is an inherited blood disorder with reduced blood-carrying capacity. It is associated with a tendency to form microclots in blood vessels, leading to painful episodes known as a vaso-occlusive crisis. Rivipansel is a pan-selectin inhibitor being studied for the treatment of a vaso-occlusive crisis in patients with sickle cell disease. METHODS: A population pharmacokinetic model of rivipansel plasma and urine concentrations was constructed using a two-compartment model and data from nine different clinical studies. Creatinine clearance was calculated using the Schwartz formula for children and the Chronic Kidney Disease Epidemiology Collaboration formula for adults. Urine volume and concentration of the study drug in urine from subjects in five clinical studies were used to estimate renal and nonrenal clearance. RESULTS: Rivipansel drug concentrations were well described by the model. The post hoc estimates of average steady-state concentrations were predicted to be similar for the adult and pediatric cohorts of the pivotal phase III study. Parameter estimates showed almost exclusively renal excretion of rivipansel, which is consistent with the known properties of the drug. CONCLUSIONS: The pharmacokinetics of rivipansel was well characterized by a two-compartment population pharmacokinetic model. Our results illustrate the important role of simulations in optimizing a potential drug dosing regimen for patients with sickle cell disease and progressive renal impairment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40268-021-00346-3. |
format | Online Article Text |
id | pubmed-8206303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-82063032021-07-01 Population Pharmacokinetic Analysis of Rivipansel in Healthy Subjects and Subjects with Sickle Cell Disease Nayak, Satyaprakash Tammara, Brinda Harnisch, Lutz O. Drugs R D Original Research Article BACKGROUND: Sickle cell disease is an inherited blood disorder with reduced blood-carrying capacity. It is associated with a tendency to form microclots in blood vessels, leading to painful episodes known as a vaso-occlusive crisis. Rivipansel is a pan-selectin inhibitor being studied for the treatment of a vaso-occlusive crisis in patients with sickle cell disease. METHODS: A population pharmacokinetic model of rivipansel plasma and urine concentrations was constructed using a two-compartment model and data from nine different clinical studies. Creatinine clearance was calculated using the Schwartz formula for children and the Chronic Kidney Disease Epidemiology Collaboration formula for adults. Urine volume and concentration of the study drug in urine from subjects in five clinical studies were used to estimate renal and nonrenal clearance. RESULTS: Rivipansel drug concentrations were well described by the model. The post hoc estimates of average steady-state concentrations were predicted to be similar for the adult and pediatric cohorts of the pivotal phase III study. Parameter estimates showed almost exclusively renal excretion of rivipansel, which is consistent with the known properties of the drug. CONCLUSIONS: The pharmacokinetics of rivipansel was well characterized by a two-compartment population pharmacokinetic model. Our results illustrate the important role of simulations in optimizing a potential drug dosing regimen for patients with sickle cell disease and progressive renal impairment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40268-021-00346-3. Springer International Publishing 2021-05-16 2021-06 /pmc/articles/PMC8206303/ /pubmed/33993463 http://dx.doi.org/10.1007/s40268-021-00346-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Original Research Article Nayak, Satyaprakash Tammara, Brinda Harnisch, Lutz O. Population Pharmacokinetic Analysis of Rivipansel in Healthy Subjects and Subjects with Sickle Cell Disease |
title | Population Pharmacokinetic Analysis of Rivipansel in Healthy Subjects and Subjects with Sickle Cell Disease |
title_full | Population Pharmacokinetic Analysis of Rivipansel in Healthy Subjects and Subjects with Sickle Cell Disease |
title_fullStr | Population Pharmacokinetic Analysis of Rivipansel in Healthy Subjects and Subjects with Sickle Cell Disease |
title_full_unstemmed | Population Pharmacokinetic Analysis of Rivipansel in Healthy Subjects and Subjects with Sickle Cell Disease |
title_short | Population Pharmacokinetic Analysis of Rivipansel in Healthy Subjects and Subjects with Sickle Cell Disease |
title_sort | population pharmacokinetic analysis of rivipansel in healthy subjects and subjects with sickle cell disease |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206303/ https://www.ncbi.nlm.nih.gov/pubmed/33993463 http://dx.doi.org/10.1007/s40268-021-00346-3 |
work_keys_str_mv | AT nayaksatyaprakash populationpharmacokineticanalysisofrivipanselinhealthysubjectsandsubjectswithsicklecelldisease AT tammarabrinda populationpharmacokineticanalysisofrivipanselinhealthysubjectsandsubjectswithsicklecelldisease AT harnischlutzo populationpharmacokineticanalysisofrivipanselinhealthysubjectsandsubjectswithsicklecelldisease |