Impact of Genetic Variation on Pravastatin Systemic Exposure in Pediatric Hypercholesterolemia

Clin Pharmacol Ther. 2019 Jun;105(6):1501-1512. doi: 10.1002/cpt.1330. Epub 2019 Feb 25.


This study investigated the impact of SLCO1B1 genotype on pravastatin systemic exposure in children and adolescents with hypercholesterolemia. Participants (8-20 years) with at least one allelic variant of SLCO1B1 c.521T>C (521TC, n = 15; 521CC, n = 2) and wild-type controls (521TT, n = 15) completed a single oral dose pharmacokinetic study. Interindividual variability of pravastatin acid (PVA) exposure within SLCO1B1 genotype groups exceeded the approximately twofold difference in mean PVA exposure observed between SLCO1B1 genotype groups (P > 0.05, q > 0.10). The 3'α-iso-pravastatin acid and lactone isomer formation in the acidic environment of the stomach prior to absorption also was variable and affected PVA exposure in all genotype groups. The SLCO1B1 c.521 gene variant contributing to variability in systemic exposure to PVA in our pediatric cohort was comparable to previous studies in adults. However, other demographic and physicochemical factors seem to also contribute to interindividual variability in the dose-exposure relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Female
  • Genetic Variation / genetics*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / blood*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypercholesterolemia / blood*
  • Hypercholesterolemia / drug therapy
  • Hypercholesterolemia / genetics*
  • Liver-Specific Organic Anion Transporter 1 / genetics*
  • Male
  • Pravastatin / blood*
  • Pravastatin / therapeutic use


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Liver-Specific Organic Anion Transporter 1
  • SLCO1B1 protein, human
  • Pravastatin