biostudies-literatureGregory BJNational Institutes of HealthNIGMS NIH HHS547-553https://www.ebi.ac.uk/biostudies/studies/S-EPMC5646416biostudies-literatureUnknown42(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-menopausal women. All of the 14 subjects were sampled for pharmacokinetic (PK) analyses and retrospectively genotyped for OATP1B1 c.521T>C (rs 4149056).<h4>Results and discussion</h4>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 AUC_0-8 between the OATP1B1 genotype groups. Our data also showed statistically significant differences (P=.04) in the plasma AUC_0-8 of 17-hydroexemestane (the major biologically active metabolite) between the OATP1B1 genotype groups.<h4>What is new and conclusion</h4>Our data suggest that the OAPTP1B1 c.521T>C SNP may influence exemestane pharmacokinetics in humans.Journal of clinical pharmacy and therapeuticsImpact of the OATP1B1 c.521T>C single nucleotide polymorphism on the pharmacokinetics of exemestane in healthy post-menopausal female volunteers.PMC5646416P20 GM103429P20GM103429Kamdem LKGregory BJChen SMMurphy MAAtchley DHfalseImpact of the OATP1B1 c.521T>C single nucleotide polymorphism on the pharmacokinetics of exemestane in healthy post-menopausal female volunteers.<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-menopausal women. All of the 14 subjects were sampled for pharmacokinetic (PK) analyses and retrospectively genotyped for OATP1B1 c.521T>C (rs 4149056).<h4>Results and discussion</h4>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 AUC_0-8 between the OATP1B1 genotype groups. Our data also showed statistically significant differences (P=.04) in the plasma AUC_0-8 of 17-hydroexemestane (the major biologically active metabolite) between the OATP1B1 genotype groups.<h4>What is new and conclusion</h4>Our data suggest that the OAPTP1B1 c.521T>C SNP may influence exemestane pharmacokinetics in humans.2017-01-01T00:00:00Z2017 Oct2024-11-08T15:08:26.484Z2019-03-26T23:58:48ZS-EPMC56464162886865410.1111/jcpt.12569