OBJECTIVE The purpose of the present study was to investigate the impact of fluvas-tatin formulation on the
pharmacokinetics-genetic polymorphis relationship.
METHODS We compared the difference between the
pharmacokinetics of
fluvastatin as an extended-release (ER) 80 mg
tablet and an immediate-release(IR)40 mg
capsule in terms of
drug metabolism enzyme and transporter ge-netic polymorphisms. In this open-label, randomized, two-period, two-
treatment,
crossover study, ef-fects of BCRP, SLCO1B1, MDR1,
CYP2C9, and
CYP3A5 polymorphisms on the
pharmacokinetics of
fluvastatin were analyzed in 24 healthy individuals.Each
treatment duration was 7 days with a washout period of 7 days between the crossover.
Serum concentration of
fluvastatin was evaluated using
high-performance liquid chromatography-
tandem mass spectrometry. RESULTS The SLCO1B1 T521C
genotype had no statistically significant effect on IR 40 mg
capsule of fluvastatinafter single or
repeated doses.However,for the ER 80 mg
tablet,the SLCO1B1 T521C
genotype correlated with the AUC0-24of repeat doses (P=0.01). The
CYP2C9*3
genotype correlated with the AUC0- 24after the first
dose IR 40 mg
capsule (P<0.05); however, the difference between
CYP2C9*1/*1 and
CYP2C9*1/*3 was not statistically significant after
repeated doses. CONCLUSION The effect of SLCO1B1 T521C on fluvas-tatin exposure was observed and was more profound in ER and
repeated dose administration than in IR and
single dose administration.We recommend that formulation should be incorporated into
future pharmacogenomics studies and clinical implication guidelines.