PMID- 36378297
OWN - NLM
STAT- MEDLINE
DCOM- 20230109
LR  - 20230111
IS  - 1432-1041 (Electronic)
IS  - 0031-6970 (Linking)
VI  - 79
IP  - 1
DP  - 2023 Jan
TI  - Impact of trough abiraterone level on adverse events in patients with prostate 
      cancer treated with abiraterone acetate.
PG  - 89-98
LID - 10.1007/s00228-022-03420-0 [doi]
AB  - PURPOSE: We assessed the impact of plasma trough concentrations of abiraterone 
      (ABI) and its metabolite Delta4-abiraterone (D4A) and related polymorphisms on 
      adverse events (AEs) in patients with metastatic prostate cancer who received 
      abiraterone acetate (AA). METHODS: This prospective study enrolled patients with 
      advanced prostate cancer treated with AA between 2016 and 2021. Plasma trough 
      concentrations of ABI and D4A were measured using high-performance liquid 
      chromatography. The impact of HSD3B1 rs1047303, SRD5A2 rs523349, and cytochrome 
      P450 family 3A member 4 rs2242480 polymorphisms on plasma concentrations of ABI 
      and D4A and the incidence of AEs were also assessed. RESULTS: In 68 patients 
      treated with AA, the median ABI and D4A concentrations were 18.1 and 0.94 ng/mL, 
      respectively. The high plasma trough concentration of ABI (>/= 20.6 ng/mL) was 
      significantly associated with the presence of any AE and its independent risk 
      factor based on multivariable analysis (odds ratio, 7.20; 95% confidence interval 
      (CI): 2.20-23.49). Additionally, a high plasma trough concentration of ABI was an 
      independent risk factor of time to withdraw AA (hazard ratio, 4.89; 95% CI: 
      1.66-14.38). The risk alleles of three polymorphisms were not statistically 
      associated with the ABI and D4A concentrations and the incidence of AEs. 
      CONCLUSIONS: The plasma trough concentration of ABI is associated with the 
      presence of AEs and treatment failure after AA administration. ABI concentration 
      monitoring may be useful in patients with prostate cancer who received AA.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Takahashi, Yoshiko
AU  - Takahashi Y
AD  - Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, 
      Akita, 010-8543, Japan.
FAU - Narita, Shintaro
AU  - Narita S
AD  - Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, 
      Akita, 010-8543, Japan. naritashintaro@gmail.com.
FAU - Shiota, Masaki
AU  - Shiota M
AD  - Department of Urology, Graduate School of Medical Sciences, Kyushu University, 
      Fukuoka, Japan.
FAU - Miura, Masatomo
AU  - Miura M
AD  - Department of Pharmacy, Akita University Hospital, Akita, Japan.
FAU - Kagaya, Hideaki
AU  - Kagaya H
AD  - Department of Pharmacy, Akita University Hospital, Akita, Japan.
FAU - Kashima, Soki
AU  - Kashima S
AD  - Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, 
      Akita, 010-8543, Japan.
FAU - Yamamoto, Ryohei
AU  - Yamamoto R
AD  - Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, 
      Akita, 010-8543, Japan.
FAU - Nara, Taketoshi
AU  - Nara T
AD  - Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, 
      Akita, 010-8543, Japan.
FAU - Huang, Mingguo
AU  - Huang M
AD  - Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, 
      Akita, 010-8543, Japan.
FAU - Numakura, Kazuyuki
AU  - Numakura K
AD  - Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, 
      Akita, 010-8543, Japan.
FAU - Saito, Mitsuru
AU  - Saito M
AD  - Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, 
      Akita, 010-8543, Japan.
FAU - Eto, Masatoshi
AU  - Eto M
AD  - Department of Urology, Graduate School of Medical Sciences, Kyushu University, 
      Fukuoka, Japan.
FAU - Habuchi, Tomonori
AU  - Habuchi T
AD  - Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, 
      Akita, 010-8543, Japan.
LA  - eng
PT  - Journal Article
DEP - 20221115
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
RN  - EM5OCB9YJ6 (Abiraterone Acetate)
RN  - G819A456D0 (abiraterone)
RN  - 0 (Androstenes)
RN  - EC 1.3.99.5 (SRD5A2 protein, human)
RN  - 0 (Membrane Proteins)
RN  - EC 1.3.99.5 (3-Oxo-5-alpha-Steroid 4-Dehydrogenase)
SB  - IM
MH  - Male
MH  - Humans
MH  - *Abiraterone Acetate/adverse effects
MH  - *Prostatic Neoplasms, Castration-Resistant/drug therapy/genetics
MH  - Prospective Studies
MH  - Androstenes
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Membrane Proteins/therapeutic use
MH  - 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/therapeutic use
OTO - NOTNLM
OT  - Abiraterone acetate
OT  - Adverse events
OT  - D4A
OT  - Polymorphisms
OT  - Prostate cancer
OT  - Trough concentration
EDAT- 2022/11/16 06:00
MHDA- 2023/01/10 06:00
CRDT- 2022/11/15 11:33
PHST- 2022/09/24 00:00 [received]
PHST- 2022/11/05 00:00 [accepted]
PHST- 2022/11/16 06:00 [pubmed]
PHST- 2023/01/10 06:00 [medline]
PHST- 2022/11/15 11:33 [entrez]
AID - 10.1007/s00228-022-03420-0 [pii]
AID - 10.1007/s00228-022-03420-0 [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 2023 Jan;79(1):89-98. doi: 10.1007/s00228-022-03420-0. Epub 
      2022 Nov 15.