Differentiating the Sodium-Glucose Cotransporter 1 Inhibition Capacity of Canagliflozin vs. Dapagliflozin and Empagliflozin Using Quantitative Systems Pharmacology Modeling.
CPT Pharmacometrics Syst Pharmacol
; 9(4): 222-229, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-32064793
ABSTRACT
The aim of this research was to differentiate dapagliflozin, empagliflozin, and canagliflozin based on their capacity to inhibit sodium-glucose cotransporter (SGLT) 1 and 2 in patients with type 2 diabetes using a previously developed quantitative systems pharmacology model of renal glucose filtration, reabsorption, and excretion. The analysis was based on pooled, mean study-level data on 24-hour urinary glucose excretion, average daily plasma glucose, and estimated glomerular filtration rate collected from phase I and II clinical trials of SGLT2 inhibitors. Variations in filtered glucose across clinical studies were shown to drive the apparent differences in the glucosuria dose-response relationships among the gliflozins. A normalized dose-response analysis demonstrated similarity of dapagliflozin and empagliflozin, but not canagliflozin. At approved doses, SGLT1 inhibition by canagliflozin but not dapagliflozin or empagliflozin contributed to ~ 10% of daily urinary glucose excretion.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Benzidrílicos
/
Canagliflozina
/
Inibidores do Transportador 2 de Sódio-Glicose
/
Glucosídeos
Limite:
Humans
Idioma:
En
Revista:
CPT Pharmacometrics Syst Pharmacol
Ano de publicação:
2020
Tipo de documento:
Article