Impact of Older Age on the Exposure of Paclitaxel: a Population Pharmacokinetic Study.
Pharm Res
; 36(2): 33, 2019 Jan 07.
Article
em En
| MEDLINE
| ID: mdl-30617624
ABSTRACT
PURPOSE:
Limited available data suggest that older patients are more prone to develop paclitaxel-induced toxicity than their younger peers. It remains unclear whether this is related to age-dependent pharmacokinetics (PK) of paclitaxel. Primary objective of this study was to determine the influence of older age on the PK of paclitaxel.METHODS:
PK data of patients aged ≥70 years who received paclitaxel intravenously at the Netherlands Cancer Institute (NKI) and the Radboud University Medical Center between September 2012 and May 2017 were collected. These prospectively collected data were pooled with previously published databases from multiple clinical trials conducted at the NKI and Erasmus MC Cancer Institute. A previously developed 3-compartment population PK model with saturable distribution and elimination was used to describe paclitaxel plasma concentration-time data. Hereafter, influence of age on paclitaxel PK was assessed in a previously established full covariate model.RESULTS:
In total, paclitaxel PK data from 684 patients were available, consisting of 166 patients ≥70 years (24%). Median age of the cohort was 61 years (range 18 to 84 years). The impact of age, either treated as a continuous or dichotomous covariate (<70 versus ≥70 years), on the elimination of paclitaxel was only marginal but statistically significant (both p < 0.001 with no clinically relevant decrease in interindividual variability). For a typical patient, maximal elimination capacity decreased by only 5% for a 10-year increment of age.CONCLUSION:
In this extensive multi-center dataset, which included a considerable number of older patients, older age had no clinically relevant impact on paclitaxel PK.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paclitaxel
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Modelos Biológicos
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Neoplasias
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Antineoplásicos Fitogênicos
Tipo de estudo:
Observational_studies
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Prognostic_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Holanda