Recent advances in pharmacokinetic characteristics and physiological pharmacokinetic modeling of small interfering RNA (siRNA) drugs

VernacularTitle:小干扰RNA (siRNA) 药物药代动力学特征及生理药代动力学建模现状
Author: Qian LI ; Rui CHEN ; Pei HU
Publication Type:Research Article
Keywords: RNA interference; small interfering RNA; pharmacokinetics; physiological pharmacokinetics; modeling; ey parameter
From: Acta Pharmaceutica Sinica 2022;57(10):3146-3156
CountryChina
Language:Chinese
Abstract: Small interfering RNAs (siRNAs) are an emerging class of RNA interference (RNAi) therapeutics with unique pharmacokinetic properties. Five siRNA drugs based on two delivery systems have been approved, and an increasing number of siRNA drugs have already moved to the clinical study phase. Physiologically-based pharmacokinetic (PBPK) modeling is a useful tool and has been demonstrated to have wide ranging utility in drug development and regulatory review. However, PBPK modeling is still in its infancy in guiding the development of siRNA-based drugs in the context of its widespread use in small and large molecule areas. This article reviews the pharmacokinetic profiles of siRNA drugs, outlines the current state of PBPK model building in siRNA drug development, and describes the key parameters required for model building. This article provides insights into the future applications of PBPK models and for optimizing the key parameters when building the model for siRNA drug development.