Influence of OATP1B1 and BCRP polymorphisms on the pharmacokinetics and pharmacodynamics of rosuvastatin in elderly and young Korean subjects.
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ABSTRACT: A lack of information regarding whether genetic polymorphisms of SLCO1B1 and ABCG2 affect the pharmacokinetics (PKs)/pharmacodynamics (PDs) of rosuvastatin in elderly subjects prevents optimal individualized pharmacotherapy of rosuvastatin in clinical settings. This study aimed to investigate the effect of age and genetic polymorphisms and possible differences in genetic effects on the PKs/PDs of rosuvastatin between elderly and young subjects. Two separate clinical studies designed as open-label, one-sequence studies with multiple-dose administration for elderly (n?=?20) and young (n?=?32) subjects were conducted. All subjects received 20?mg of rosuvastatin once daily for 21 days. The exposure to rosuvastatin, characterized by the area under the time curve (AUC), increased by 23% in the elderly subjects compared with that of young subjects, which was not significant. When compared to the subjects with breast cancer resistance protein (BCRP) normal function, the exposure to rosuvastatin increased by 44% in young subjects (p?=?0.0021) with BCRP intermediate function (IF) and by 35% and 59% (p?>?0.05 for both) in elderly subjects with BCRP IF and low function, respectively. SLCO1B1 521T?>?C was also partially associated with a higher AUC of rosuvastatin in young subjects and a less pronounced increasing trend in elderly subjects (p?>?0.05 for both). The lipid-lowering effect of rosuvastatin was less pronounced in the elderly subjects than in the young subjects, and genetic polymorphisms of neither SLCO1B1 nor ABCG2 significantly affected the PDs of rosuvastatin. The ABCG2 421C?>?A polymorphism was associated with the PKs of rosuvastatin and was identified as a more important determinant than the SLCO1B1 521T?>?C polymorphism in both elderly and young subjects.
SUBMITTER: Kim Y
PROVIDER: S-EPMC6923423 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
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