TY - JOUR
T1 - Impact of age on exposure to oral antiandrogen therapies in clinical practice
AU - Crombag, Marie Rose B.S.
AU - van Nuland, Merel
AU - Bergman, Andries M.
AU - Rosing, Hilde
AU - Schellens, Jan H.M.
AU - Huitema, Alwin D.R.
AU - Beijnen, Jos H.
N1 - Publisher Copyright:
© 2018, Springer Nature Limited.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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 and methods: 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.
AB - 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 and methods: 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.
UR - http://www.scopus.com/inward/record.url?scp=85054395862&partnerID=8YFLogxK
U2 - 10.1038/s41391-018-0096-z
DO - 10.1038/s41391-018-0096-z
M3 - Article
C2 - 30279580
AN - SCOPUS:85054395862
SN - 1365-7852
VL - 22
SP - 168
EP - 175
JO - Prostate Cancer and Prostatic Diseases
JF - Prostate Cancer and Prostatic Diseases
IS - 1
ER -