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.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |