Impact of SLCO1B1 Genetic Variation on Rosuvastatin Systemic Exposure in Pediatric Hypercholesterolemia

Clin Transl Sci. 2020 May;13(3):628-637. doi: 10.1111/cts.12749. Epub 2020 Mar 9.


This study investigated the impact of SLCO1B1 genotype on rosuvastatin systemic exposure in hypercholesterolemic children and adolescents. Participants (8-21 years) with at least one allelic variant of SLCO1B1 c.521T>C (521TC, n = 13; 521CC, n = 2) and wild type controls (521TT, n = 13) completed a single oral dose pharmacokinetic study. The variability contributed by SLCO1B1 c.521 sequence variation to rosuvastatin (RVA) systemic exposure among our pediatric cohort was comparable to previous studies in adults. RVA concentration-time curve from 0-24 hours (AUC0-24 ) was 1.4-fold and 2.2-fold higher in participants with c.521TC and c.521CC genotype compared 521TT participants, respectively. Interindividual variability of RVA exposure within SLCO1B1 genotype groups exceeded the ~ 1.5-fold to 2-fold difference in mean RVA exposure observed among SLCO1B1 genotype groups, suggesting that other factors also contribute to interindividual variability in the rosuvastatin dose-exposure relationship. A multivariate model performed confirmed SLCO1B1 c.521T>C genotype as the primary factor contributing to RVA systemic exposure in this pediatric cohort, accounting for ~ 30% of the variability RVA AUC0-24 . However, of the statins investigated to date in the pediatric population, RVA has the lowest magnitude of variability in systemic exposure.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Female
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / genetics
  • Liver-Specific Organic Anion Transporter 1 / genetics*
  • Liver-Specific Organic Anion Transporter 1 / metabolism
  • Male
  • Pharmacogenomic Variants
  • Polymorphism, Single Nucleotide
  • Rosuvastatin Calcium / administration & dosage
  • Rosuvastatin Calcium / pharmacokinetics*
  • Young Adult


  • Liver-Specific Organic Anion Transporter 1
  • SLCO1B1 protein, human
  • Rosuvastatin Calcium