Effects of age and sex on the single-dose pharmacokinetics and pharmacodynamics of apixaban.
Clin Pharmacokinet
; 54(6): 651-62, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25573421
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Piridonas
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Inibidores do Fator Xa
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article