Impact of the OATP1B1 c.521T>C single nucleotide polymorphism on the pharmacokinetics of exemestane in healthy post-menopausal female volunteers.
J Clin Pharm Ther
; 42(5): 547-553, 2017 Oct.
Article
in En
| MEDLINE
| ID: mdl-28868654
ABSTRACT
WHAT IS KNOWN AND OBJECTIVE:
OATP1B1 mediates the transport of a diverse range of amphiphilic organic compounds that include bile acids, steroid conjugates and hormones. This retrospective pharmacogenetic study was conducted to assess the impact of the OATP1B1 c.521T>C single nucleotide polymorphism (SNP) on the pharmacokinetics of the steroidal aromatase inhibitor drug exemestane in healthy volunteers.METHODS:
Exemestane (25 mg) was administered orally to 14 healthy post-menopausal women. All of the 14 subjects were sampled for pharmacokinetic (PK) analyses and retrospectively genotyped for OATP1B1 c.521T>C (rs 4149056). RESULTS ANDDISCUSSION:
Of the 14 subjects enrolled in the study, five were carriers of the minor C allele (OATP1B1 c.521TC+CC) and the remaining nine were carriers of the OATP1B1 c.521TT genotype. PK was assessed over 8 hours post-dosing. Our results showed statistically significant differences (P=.04) in the plasma exemestane AUC0-8 between the OATP1B1 genotype groups. Our data also showed statistically significant differences (P=.04) in the plasma AUC0-8 of 17-hydroexemestane (the major biologically active metabolite) between the OATP1B1 genotype groups. WHAT IS NEW ANDCONCLUSION:
Our data suggest that the OAPTP1B1 c.521T>C SNP may influence exemestane pharmacokinetics in humans.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Postmenopause
/
Liver-Specific Organic Anion Transporter 1
/
Aromatase Inhibitors
/
Androstadienes
Type of study:
Observational_studies
/
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
/
Middle aged
Language:
En
Journal:
J Clin Pharm Ther
Journal subject:
FARMACIA
/
TERAPEUTICA
Year:
2017
Document type:
Article
Affiliation country:
Estados Unidos