Clinical Pharmacology and Therapeutics
Clinical Pharmacology and Therapeutics
5 years ago

Impact of the OATP1B1 c.521T>C single nucleotide polymorphism on the pharmacokinetics of exemestane in healthy post-menopausal female volunteers

Impact of the OATP1B1 c.521T>C single nucleotide polymorphism on the pharmacokinetics of exemestane in healthy post-menopausal female volunteers
L. K. Kamdem, B. J. Gregory, D. H. Atchley, M. A. Murphy, S. M. Chen
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 and discussion 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 and conclusion Our data suggest that the OAPTP1B1 c.521T>C SNP may influence exemestane pharmacokinetics in humans. Significant interindividual variability has been observed in the clinical response to aromatase inhibitors. The aim of our study was to assess the impact of the OATP1B1 c. 521 T>C single nucleotide polymorphism on the pharmacokinetics of exemestane in healthy volunteers.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/jcpt.12569

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