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Effects of Age and Sex on the Single-Dose Pharmacokinetics and Pharmacodynamics of Apixaban
BACKGROUND AND OBJECTIVES: The effects of age and sex on apixaban pharmacokinetics and pharmacodynamics were studied. METHODS: This was an open-label, single-dose, 2 × 2 factorial study. Healthy young (aged 18–40 years) and elderly (aged ≥65 years) male and female subjects received a single oral 20 ...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449375/ https://www.ncbi.nlm.nih.gov/pubmed/25573421 http://dx.doi.org/10.1007/s40262-014-0228-0 |
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author | Frost, Charles E. Song, Yan Shenker, Andrew Wang, Jessie Barrett, Yu Chen Schuster, Alan Harris, Stuart I. LaCreta, Frank |
author_facet | Frost, Charles E. Song, Yan Shenker, Andrew Wang, Jessie Barrett, Yu Chen Schuster, Alan Harris, Stuart I. LaCreta, Frank |
author_sort | Frost, Charles E. |
collection | PubMed |
description | BACKGROUND AND OBJECTIVES: The effects of age and sex on apixaban pharmacokinetics and pharmacodynamics were studied. METHODS: This was an open-label, single-dose, 2 × 2 factorial study. Healthy young (aged 18–40 years) and elderly (aged ≥65 years) male and female subjects received a single oral 20 mg dose of apixaban. Blood and urine samples were collected for pharmacokinetic and pharmacodynamic (blood only) analyses. Subjects were monitored for adverse events throughout the study. RESULTS: Seventy-nine subjects were enrolled into four groups: young males (n = 20), elderly males (n = 20), young females (n = 20) and elderly females (n = 19). Age did not affect the maximum observed plasma concentration (C (max)). The mean area under the concentration–time curve from time zero extrapolated to infinite time (AUC(∞)) was 32 % greater in elderly subjects than in young subjects. The mean C (max) and AUC(∞) values were 18 and 15 % higher, respectively, in females than in males. The time course of the mean international normalized ratio (INR), modified prothrombin time (mPT) and anti-Xa activity tracked the apixaban concentration–time curve. All three pharmacodynamic measures exhibited a positive linear correlation with the plasma apixaban concentration. Differences in the mean INR, mPT and anti-Xa activity between age and sex groups were small (<15 % at the maximum mean values) and were generally related to pharmacokinetic differences. However, anti-Xa activity demonstrated less variability than the INR or mPT, and may have utility as a bioassay for apixaban. Apixaban was well tolerated, with no serious adverse events. CONCLUSION: There were no clinically meaningful age- or sex-related differences in the pharmacokinetics and pharmacodynamics of apixaban that would require dose modification on the basis of age or sex alone. |
format | Online Article Text |
id | pubmed-4449375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-44493752015-06-04 Effects of Age and Sex on the Single-Dose Pharmacokinetics and Pharmacodynamics of Apixaban Frost, Charles E. Song, Yan Shenker, Andrew Wang, Jessie Barrett, Yu Chen Schuster, Alan Harris, Stuart I. LaCreta, Frank Clin Pharmacokinet Original Research Article BACKGROUND AND OBJECTIVES: The effects of age and sex on apixaban pharmacokinetics and pharmacodynamics were studied. METHODS: This was an open-label, single-dose, 2 × 2 factorial study. Healthy young (aged 18–40 years) and elderly (aged ≥65 years) male and female subjects received a single oral 20 mg dose of apixaban. Blood and urine samples were collected for pharmacokinetic and pharmacodynamic (blood only) analyses. Subjects were monitored for adverse events throughout the study. RESULTS: Seventy-nine subjects were enrolled into four groups: young males (n = 20), elderly males (n = 20), young females (n = 20) and elderly females (n = 19). Age did not affect the maximum observed plasma concentration (C (max)). The mean area under the concentration–time curve from time zero extrapolated to infinite time (AUC(∞)) was 32 % greater in elderly subjects than in young subjects. The mean C (max) and AUC(∞) values were 18 and 15 % higher, respectively, in females than in males. The time course of the mean international normalized ratio (INR), modified prothrombin time (mPT) and anti-Xa activity tracked the apixaban concentration–time curve. All three pharmacodynamic measures exhibited a positive linear correlation with the plasma apixaban concentration. Differences in the mean INR, mPT and anti-Xa activity between age and sex groups were small (<15 % at the maximum mean values) and were generally related to pharmacokinetic differences. However, anti-Xa activity demonstrated less variability than the INR or mPT, and may have utility as a bioassay for apixaban. Apixaban was well tolerated, with no serious adverse events. CONCLUSION: There were no clinically meaningful age- or sex-related differences in the pharmacokinetics and pharmacodynamics of apixaban that would require dose modification on the basis of age or sex alone. Springer International Publishing 2015-01-09 2015 /pmc/articles/PMC4449375/ /pubmed/25573421 http://dx.doi.org/10.1007/s40262-014-0228-0 Text en © The Author(s) 2015 https://creativecommons.org/licenses/by-nc/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Research Article Frost, Charles E. Song, Yan Shenker, Andrew Wang, Jessie Barrett, Yu Chen Schuster, Alan Harris, Stuart I. LaCreta, Frank Effects of Age and Sex on the Single-Dose Pharmacokinetics and Pharmacodynamics of Apixaban |
title | Effects of Age and Sex on the Single-Dose Pharmacokinetics and Pharmacodynamics of Apixaban |
title_full | Effects of Age and Sex on the Single-Dose Pharmacokinetics and Pharmacodynamics of Apixaban |
title_fullStr | Effects of Age and Sex on the Single-Dose Pharmacokinetics and Pharmacodynamics of Apixaban |
title_full_unstemmed | Effects of Age and Sex on the Single-Dose Pharmacokinetics and Pharmacodynamics of Apixaban |
title_short | Effects of Age and Sex on the Single-Dose Pharmacokinetics and Pharmacodynamics of Apixaban |
title_sort | effects of age and sex on the single-dose pharmacokinetics and pharmacodynamics of apixaban |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449375/ https://www.ncbi.nlm.nih.gov/pubmed/25573421 http://dx.doi.org/10.1007/s40262-014-0228-0 |
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