Impact of Genetic Variation on Pravastatin Systemic Exposure in Pediatric Hypercholesterolemia.
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
02
08
2018
accepted:
20
11
2018
pubmed:
15
12
2018
medline:
5
3
2020
entrez:
15
12
2018
Statut:
ppublish
Résumé
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.
Substances chimiques
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Liver-Specific Organic Anion Transporter 1
0
SLCO1B1 protein, human
0
Pravastatin
KXO2KT9N0G
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1501-1512Informations de copyright
© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.