SLCO1B1 Genetic Variation Influence on Atorvastatin Systemic Exposure in Pediatric Hypercholesterolemia.
Genes (Basel)
; 15(1)2024 01 15.
Article
en En
| MEDLINE
| ID: mdl-38254988
ABSTRACT
This clinical study examined the influence of SLCO1B1 c.521T>C (rs4149056) on plasma atorvastatin concentrations in pediatric hypercholesterolemia. The participants (8-21 years), including heterozygous (c.521T/C, n = 13), homozygous (c.521C/C, n = 2) and controls (c.521T/T, n = 13), completed a single-oral-dose pharmacokinetic study. Similar to in adults, the atorvastatin (AVA) area-under-concentration-time curve from 0 to 24 h (AUC0-24) was 1.7-fold and 2.8-fold higher in participants with c.521T/C and c.521C/C compared to the c.521T/T participants, respectively. The inter-individual variability in AVA exposure within these genotype groups ranged from 2.3 to 4.8-fold, indicating that additional factors contribute to the inter-individual variability in the AVA dose-exposure relationship. A multivariate model reinforced the SLCO1B1 c.521T>C variant as the central factor contributing to AVA systemic exposure in this pediatric cohort, accounting for ~65% of the variability in AVA AUC0-24. Furthermore, lower AVA lactone concentrations in participants with increased body mass index contributed to higher exposure within the c.521T/T and c.521T/C genotype groups. Collectively, these factors contributing to higher systemic exposure could increase the risk of toxicity and should be accounted for when individualizing the dosing of atorvastatin in eligible pediatric patients.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Hipercolesterolemia
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Child
/
Humans
Idioma:
En
Revista:
Genes (Basel)
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos