两种定量分析法在成人-儿童转化中的应用

Application of two quantitative analysis methods in dose conversion from adult to child

目的通过建立成人-儿童转化模型,为儿童临床用药提供指导性的建议,使得最大程度的减少儿童群体临床重复试验研究,降低儿童用药风险。方法以阿奇霉素为例,根据临床现有的成人药代动力学参数为基础,以儿童文献中的数据作为外部验证,对两种转化方法进行计算,得到参数的相对偏差和相对标准误差。结果通过异速模型、异速+成熟模型模拟出儿童相关的药代动力学参数,计算异速模型的ρmax和tmax的相对偏差分别为-0.49、-0.23;相对标准误差分别为0.50、0.35。异速+成熟模型的ρmax和tmax的相对偏差分别为-0.48、-0.13;相对标准误差分别为0.50、0.33。结论本研究仅仅是介绍了两种可行的转化思路,并不代表在所有药物临床试验前研究中都可行,要根据具体情况,建立可行的转化方法。

Objective To established an adult-child dose conversion model,to provide guiding suggestions for children′s clinical medication,to minimize the repeated clinical trials of children′s groups and to reduce the risk of drug use for children.Methods Taking azithromycin as an example,the relative bias and relative standard error(RSE)of the two conversion methods were calculated with the clinically available adult pharmacokinetic parameters as the basic information and the data in children′s literature as the external verification.Results The pharmacokinetic parameters of the children were simulated by allometric model and allometric+mature model.The relative bias ofρmax and tmax of allometric model were-0.49 and-0.23,respectively.The relative standard errors were 0.50 and 0.35,respectively.The relative bias ofρmax and tmax for allometric+mature model were-0.48 and-0.13,respectively.The relative standard errors were 0.50 and 0.33,respectively.Conclusion This study only introduces two feasible conversion ideas,which does not mean that it is feasible in all pre-clinical trials of drugs.It is necessary to establish feasible conversion methods according to specific conditions.