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

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 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.

SUBMITTER: Gregory BJ

PROVIDER: S-EPMC5646416 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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

Gregory B J BJ Chen S M SM Murphy M A MA Atchley D H DH Kamdem L K LK

Journal of clinical pharmacy and therapeutics 20170729 5

<h4>What is known and objective</h4>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.<h4>Methods</h4>Exemestane (25 mg) was administered orally to 14 healthy post-menopausa ...[more]

PMID: 28868654

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Dataset Information

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

Publications

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

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