Format

Send to

Choose Destination
Clin Pharmacol Ther. 2018 Dec 14. doi: 10.1002/cpt.1330. [Epub ahead of print]

Impact of Genetic Variation on Pravastatin Systemic Exposure in Pediatric Hypercholesterolemia.

Author information

1
Ward Family Heart Center, Children's Mercy, Kansas City, Missouri, USA.
2
Division of Clinical Pharmacology, Medical Toxicology and Therapeutic Innovation, Children's Mercy, Kansas City, Missouri, USA.
3
Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA.
4
Health Services & Outcomes Research, Children's Mercy, Kansas City, Missouri, USA.

Abstract

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.

PMID:
30549267
DOI:
10.1002/cpt.1330

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center