Impact of the OATP1B1 c.521T>C Single Nucleotide Polymorphism on the Pharmacokinetics of Exemestane in Healthy Post-Menopausal Female Volunteers
Journal of Clinical Pharmacy and Therapeutics
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 OATP1B1c.521T>C single nucleotide polymorphism (SNP) on the pharmacokinetics of the steroidal aromatase inhibitor drug exemestane in healthyvolunteers.
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.
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John Wiley & Sons Ltd
Gregory, B. J., Chen, S. M., Murphy, M. A., Atchley, D. H., & Kamdem, L. K. (2017). Impact of the OATP1B1 c.521T>C Single Nucleotide Polymorphism on the Pharmacokinetics of Exemestane in Healthy Post-Menopausal Female Volunteers. Journal of Clinical Pharmacy and Therapeutics, 42 (5), 547-553. http://dx.doi.org/10.1111/jcpt.12569