Model‐Informed Pediatric Dose Selection for Dapagliflozin by Incorporating Developmental Changes

• Published in: CPT: pharmacometrics and systems pharmacology Vol. 10; no. 2; pp. 108 - 118
• Main Authors: Jo, Heeseung, Pilla Reddy, Venkatesh, Parkinson, Joanna, Boulton, David W., Tang, Weifeng
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.02.2021; John Wiley and Sons Inc; Wiley
• Subjects: Administration, Oral; Adolescent; Adults; Age groups; Antibiotics, Antitubercular - administration & dosage; Antibiotics, Antitubercular - adverse effects; Antibiotics, Antitubercular - pharmacokinetics; Antidiabetics; Area Under Curve; Benzhydryl Compounds - pharmacokinetics; Cardiovascular disease; Child; Child, Preschool; Clinical trials; Computer Simulation; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - adverse effects; Cyclooxygenase Inhibitors - pharmacokinetics; Cytochrome; Diabetes; Dose-Response Relationship, Drug; Drug dosages; Drug Interactions; Enzyme kinetics; FDA approval; Female; Glucose; Glucosides - pharmacokinetics; Glucuronosyltransferase - metabolism; Healthy Volunteers - statistics & numerical data; Hepatic Insufficiency - drug therapy; Humans; Infant; Infant, Newborn; Male; Mefenamic Acid - administration & dosage; Mefenamic Acid - adverse effects; Mefenamic Acid - pharmacokinetics; Metabolism; Metabolites; Models, Biological; Pediatrics; Pharmacokinetics; Physiology; Plasma; Population; Predictive Value of Tests; R&D; Regulatory approval; Renal Insufficiency - drug therapy; Research & development; Rifampin - administration & dosage; Rifampin - adverse effects; Rifampin - pharmacokinetics; Sodium-Glucose Transporter 2 Inhibitors - pharmacokinetics; UDP-Glucuronosyltransferase 1A9 - metabolism; United States > US

This analysis reports a quantitative modeling and simulation approach for oral dapagliflozin, a primarily uridine diphosphate‐glucuronosyltransferase (UGT)–metabolized human sodium‐glucose cotransporter 2 selective inhibitor. A mechanistic dapagliflozin physiologically based pharmacokinetic (PBPK) m...