Impact of age on exposure to oral antiandrogen therapies in clinical practice.
Prostate Cancer Prostatic Dis
; 22(1): 168-175, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30279580
ABSTRACT
BACKGROUND:
Oral antiandrogen therapies are predominantly used in older men, but real-life studies evaluating the impact of age on pharmacokinetic exposure are lacking. This study aims to evaluate the impact of age on the pharmacokinetic profiles of abiraterone acetate and enzalutamide in clinical practice. PATIENTS ANDMETHODS:
Retrospective observational study to evaluate the impact of age on the first steady-state sample of patients treated with abiraterone acetate or enzalutamide in routine daily clinical practice. The effect of age on target attainment was assessed.RESULTS:
For abiraterone acetate and enzalutamide, 71 and 64 patients were included, respectively. Baseline patients' characteristics and administered doses were not age-dependent. No age-related differences were observed in exposure to the main metabolites of abiraterone acetate, except for active metabolite Δ(4)-Abiraterone (D4A) with a median plasma concentration of 2.5 × 10-3 mg/L in the oldest versus 1.3 × 10-3 mg/L in the youngest age quartile (coefficient of variation, CV, 72%, p = 0.03). For enzalutamide, no significant differences in exposure were found, except for carboxylic acid enzalutamide, having a median plasma concentration of 5.8 mg/L versus 3.9 mg/L in the oldest versus the youngest age quartile (CV 66%, p = 0.03). However, this was driven by one patient aged 99 years old. Age had no significant influence on target attainment of either compound.CONCLUSIONS:
This study showed no significant impact of age on the pharmacokinetic profiles of abiraterone acetate and enzalutamide, except for the active metabolite D4A and the inactive metabolite carboxylic acid enzalutamide, both having significantly higher exposure in older males. Target attainments of abiraterone and enzalutamide were not significantly affected by age, which suggests that age has no clinically relevant impact on exposure to these oral antiandrogen therapies. However, the clinical impact of higher exposure to D4A in older males remains undetermined.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Antagonistas de Androgênios
/
Antineoplásicos
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Aged80
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Prostate Cancer Prostatic Dis
Assunto da revista:
ENDOCRINOLOGIA
/
NEOPLASIAS
/
UROLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Holanda