Summary of rosuvastatin BCRP pharmacogenomic studies and associated effect on its PK

DoseaSubject Race and GenderBCRP c.421C>A Number of subjects per GenotypeOATP1B1 PhenotypeEffect of c.421C>A SNPReference
20-mg SDAsian Chinese male7 CC, 5 CA, 2 AAAll subjects had OATP1B1 521T/T and CYP2C9*1/*1 genotypes (wild type)1.78-fold AUC increase in 421C/A and A/A genotypes (combined)bZhang et al., 2006
20-mg SDCaucasian (50% female)16 CC, 12 CA, 4 AAIndividuals with the OATP1B1 521C/C genotype not includedc1.2-fold AUC increase in 421C/A (N.S.); 2.44- and 2.3-fold AUC and Cmax increase, respectively, in 421A/AbKeskitalo et al., 2009b
5-, 10-, and 20-mg SD (1-wk washout)Asian Chinese15 CC, 15 CA, 6 AANo significant effect of CYP2C9*3 and OATP1B1 c.521T>C1.6-fold AUC increase in 421A/AdZhou et al., 2013
10 mg/day (minimum 4 wk)Asian Chinese (52% female)129 CC, 108 CA, 39 AA205 OATP1B1 521T/T and 62/5 T/C and C/C; rosuvastatin plasma concentrations affected by both BCRP 421C>A and OATPB1 521T>Ce2.2-fold increase in mean plasma concentrations in 421A/Ab,f; BCRP 421C>A (but not OATP1B1 521T>C) strongly associated with the LDL-C response to rosuvastatinLee, 2013
  • LDL-C, low-density lipoprotein cholesterol; SD, single dose.

  • a The route of administration was oral in all cases.

  • b Denotes significant change (P < 0.05).

  • c Subjects had ABCB1 1199G/G reference genotype.

  • d Dose-normalized changes (based on 5 mg).

  • e No effect of CYP2C9*1/*3 or *3/*3 on rosuvastatin PK or PD.

  • f 1.99-fold increase in mean plasma concentration of N-desmethyl rosuvastatin.