Rosuvastatin Pharmacokinetics in Asian and White Subjects Wild Type for Both OATP1B1 and BCRP Under Control and Inhibited Conditions

Abstract

The Food and Drug Administration recommends rosuvastatin dosage reductions in Asian patients because pharmacokinetic studies have demonstrated an approximate 2-fold increase in median exposure to rosuvastatin in Asian subjects compared with Caucasian controls. Yet, no explanation for this ethnic difference has been confirmed. Here we show that rosuvastatin exposure in Asians and Whites does not differ significantly when all subjects are wild-type carriers for both solute carrier organic anion transporter 1B1 *1a and ATP-binding cassette subfamily G member 2 c.421 transporters in a 2-arm, randomized, cross-over rosuvastatin pharmacokinetics study in healthy white and Asian volunteers. For single rosuvastatin doses, AUC0-48 were 92.5 (±36.2) and 83.5 (±32.2) ng/mL × h and Cmax were 10.0 (±4.1) and 7.6 (±3.0) ng/mL for Asians and Whites, respectively. When transporters were inhibited by intravenous rifampin, rosuvastatin AUC0-48 and Cmax also showed no ethnic differences. Our study suggests that both SLCO1B1 and ABCG2 polymorphisms are better predictors of rosuvastatin exposure than ethnicity alone and could be considered in precision medicine dosing of rosuvastatin.

Trial registration: ClinicalTrials.gov NCT02215174.

Keywords: ABC transporters; clinical pharmacokinetics; drug interaction; efflux pumps; hepatic transport; intestinal absorption; organic anion-transporting polypeptide transporters; race.

Conflict of interest statement

Conflicts of Interest: The authors declare no conflict of interest.

Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Rosuvastatin pharmacokinetics in 8 Asian and 7 White healthy volunteers. Mean plasma concentration of rosuvastatin (± SD) following a single oral 20mg dose of rosuvastatin. The inset depicts the same data on a semi-logarithmic scale. Similar variability in rosuvastatin AUC0–∞ between (a) White and (b) Asian subjects was noted.

Figure 2

The effect of rifampin on the pharmacokinetics of rosuvastatin in White (n=7) and Asian (n=8) healthy volunteers. Both rosuvastatin mean AUC0–48 and Cmax following a single oral dose of 20 mg rosuvastatin, with and without the administration of rifampin, in White (a and c) and Asian (b and d) healthy volunteers increased in the presence of rifampin.