Insights into drug development with quantitative systems pharmacology: A prospective case study of uncovering hyperkalemia risk in diabetic nephropathy with virtual clinical trials.
Drug Metab Pharmacokinet
; 56: 101019, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38797092
ABSTRACT
The quantitative systems pharmacology (QSP) approach is widely applied to address various essential questions in drug discovery and development, such as identification of the mechanism of action of a therapeutic agent, patient stratification, and the mechanistic understanding of the progression of disease. In this review article, we show the current landscape of the application of QSP modeling using a survey of QSP publications over 10 years from 2013 to 2022. We also present a use case for the risk assessment of hyperkalemia in patients with diabetic nephropathy treated with mineralocorticoid receptor antagonists (MRAs, renin-angiotensin-aldosterone system inhibitors), as a prospective simulation of late clinical development. A QSP model for generating virtual patients with diabetic nephropathy was used to quantitatively assess that the nonsteroidal MRAs, finerenone and apararenone, have a lower risk of hyperkalemia than the steroidal MRA, eplerenone. Prospective simulation studies using a QSP model are useful to prioritize pharmaceutical candidates in clinical development and validate mechanism-based pharmacological concepts related to the risk-benefit, before conducting large-scale clinical trials.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Diabetic Nephropathies
/
Mineralocorticoid Receptor Antagonists
/
Drug Development
/
Hyperkalemia
Limits:
Humans
Language:
En
Journal:
Drug Metab Pharmacokinet
Journal subject:
FARMACOLOGIA
/
METABOLISMO
Year:
2024
Document type:
Article
Country of publication:
Reino Unido