临床阶段药品 (Phase I/II) 的HBELs的确定

beiwei5du

临床阶段药品 (Phase I/II) 的由于数据缺乏，很难用有限的数据计算PDEs,那么可以考虑药品分类的方法，使用分级TTC方法，获取相应的HBELs
5.5  Investigational Medicinal Products
For early development (Phase I/II) investigational medicinal products (IMPs) estimation of PDEs may
be difficult based on their limited data sets. Where this is apparent, an alternative approach using
categorisation into specific default value categories e.g. based on low/high expected pharmacological
potency, low/high toxicity, genotoxicity/carcinogenicity, similar to the tiered Threshold of Toxicological
Concern approaches proposed by Kroes et al. (2004), Munro et al. (2008), and Dolan et al. (2005)2
can be considered to derive health-based exposure limits if adequately justified. Since most default
limits are defined for chronic exposure durations, a higher limit may be justified if a drug substance
shares equipment with another that is intended for short-term clinical trials (Bercu and Dolan, 2013)3
With the availability of more pharmacological and toxicological data, compound-specific limits should
be calculated as described above for the derivation of health-based exposure limits.


相关的文献：
Kroes R, Renwick A, Cheeseman M, Kleiner J, Mangelsdorf I, Piersma A, Schilter B, Schatter J, van
Schothorst F, Vos JG, Würtzen G. (2004). Structure-based thresholds of toxicological concern (TTC):
guidance for application to substances present at low levels in the diet. Fd Chem Toxicol 42, 65-83.
Munro IC, Renwick AG, Danielewska-Nikiel B (2008). The threshold of toxicological concern (TTC) in
risk assessment. Toxicol Lett 180, 151-156.
Dolan DG, Naumann BD, Sargent EV, Maier A, Dourson M (2005). Application of the threshold of
toxicological concern concept to pharmaceutical manufacturing operations. Regul Toxicol Pharmacol,
43, 1-9.

胜利者

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syhorchid

学习一下

小金库

非常感谢分享。