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

Research output: Contribution to journalArticle

Authors

  • Jonathan B. Wagner
  • Susan Abdel-Rahman
  • Andrea Gaedigk
  • Roger Gaedigk
  • Geetha Raghuveer
  • Vincent S. Staggs
  • Leon Van Haandel
  • J. Steven Leeder

External Institution(s)

  • Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation
  • University of Missouri at Kansas City
  • Ward Family Heart Center
  • Health Services and Outcomes Research

Details

Original languageEnglish (US)
Pages (from-to)628-637
Number of pages10
JournalClinical and translational science
Volume13
Issue number3
StatusPublished - May 1 2020
Peer-reviewedYes

Abstract

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.

Citation formats

APA

Wagner, J. B., Abdel-Rahman, S., Gaedigk, A., Gaedigk, R., Raghuveer, G., Staggs, V. S., ... Leeder, J. S. (2020). Impact of SLCO1B1 Genetic Variation on Rosuvastatin Systemic Exposure in Pediatric Hypercholesterolemia. Clinical and translational science, 13(3), 628-637. https://doi.org/10.1111/cts.12749

Harvard

Wagner, JB, Abdel-Rahman, S, Gaedigk, A, Gaedigk, R, Raghuveer, G, Staggs, VS, Van Haandel, L & Leeder, JS 2020, 'Impact of SLCO1B1 Genetic Variation on Rosuvastatin Systemic Exposure in Pediatric Hypercholesterolemia', Clinical and translational science, vol. 13, no. 3, pp. 628-637. https://doi.org/10.1111/cts.12749