Physiologically Based Pharmacokinetic Modelling to Predict Pharmacokinetics of Enavogliflozin, a Sodium-Dependent Glucose Transporter 2 Inhibitor, in Humans
Abstract
Enavogliflozin is a sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor approved for clinical use in South Korea. As SGLT2 inhibitors are a treatment option for patients with diabetes, enavogliflozin is expected to be prescribed in various populations. Physiologically based pharmacokinetic (PBPK) modelling can rationally predict the concentration-time profiles under altered physiological conditions. In previous studies, one of the metabolites (M1) appeared to have a metabolic ratio between 0.20 and 0.25. In this study, PBPK models for enavogliflozin and M1 were developed using published clinical trial data. The PBPK model for enavogliflozin incorporated a non-linear urinary excretion in a mechanistically arranged kidney model and a non-linear formation of M1 in the liver. The PBPK model was evaluated, and the simulated pharmacokinetic characteristics were in a two-fold range from those of the observations. The pharmacokinetic parameters of enavogliflozin were predicted using the PBPK model under pathophysiological conditions. PBPK models for enavogliflozin and M1 were developed and validated, and they seemed useful for logical prediction.
Read the paper
Related studies
- Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study
- Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study
- Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study
- Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study
- Ethnic and socioeconomic differences in SARS-CoV-2 infection: prospective cohort study using UK Biobank
- Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.