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- W2970011527 abstract "The present study investigated whether the clinical pharmacokinetics of atorvastatin can be predicted from the results of microdosing study in Japanese patients with hypercholesterolemia whose SLCO1B1 and ABCG2 polymorphisms were analyzed. Forty seven statin-naive patients clinically indicated to LDL cholesterol-lowering therapy with atorvastatin were enrolled in a two-period crossover study. Microdose (100 μg) of atorvastatin was orally administered followed by therapeutic dose (10 mg) administration. Transport studies were performed with BCRP-expressing membrane vesicles. The dose-normalized plasma AUC following the therapeutic dose of atorvastatin was positively correlated with that following its microdose, but the AUC increased more than dose proportionally from microdose to therapeutic dose. The patients carrying SLCO1B1 c.521TC showed a significantly higher AUC compared with those carrying c.521TT following the microdose (175%) and therapeutic dose (139%). On the other hand, SLCO1B1 c.388G or ABCG2 c.421A variant alleles did not significantly affect the pharmacokinetics of atorvastatin. Atorvastatin showed ATP-dependent transport in BCRP-expressing membrane vesicles and it inhibited rosuvastatin transport with Ki of 6.3 ± 2.9 μM (mean ± SD). Microdosing study appears to be feasible to roughly estimate the pharmacokinetic and pharmacogenetic profiles of atorvastatin following the oral therapeutic dose in hypercholesterolemic patients." @default.
- W2970011527 created "2019-09-05" @default.
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- W2970011527 date "2019-12-01" @default.
- W2970011527 modified "2023-10-16" @default.
- W2970011527 title "Microdosing clinical study to clarify pharmacokinetic and pharmacogenetic characteristics of atorvastatin in Japanese hypercholesterolemic patients" @default.
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- W2970011527 doi "https://doi.org/10.1016/j.dmpk.2019.08.004" @default.
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