First dose prediction is challenging in neonates. Our objective in this proof-of-concept study was to perform a pharmacokinetic (PK) bridging study from juvenile mice to neonates for drugs metabolized by CYP3A.

We selected midazolam and clindamycin as model drugs. We developed juvenile mice population PK models using NONMEM. The PK parameters of these two drugs in juvenile mice were used to bridge PK parameters in neonates using different correction methods. The bridging results were evaluated by the fold-error of 0.5- to 1.5-fold.

Simple allometry with and without a correction factor for maximum lifespan potential could be used for a bridging of clearance (CL) and volume of distribution (V_d), respectively, from juvenile mice to neonates. Simulation results demonstrated that for midazolam, 100% of clinical studies for which both the predictive CL and V_d were within 0.5- to 1.5-fold of the observed. For clindamycin, 75% and 100% of clinical studies for which the predictive CL and V_d were within 0.5- to 1.5-fold of the observed.

A PK bridging of drugs metabolized by CYP3A is feasible from juvenile mice to neonates. It could be a complement to the ADE and PBPK models to support the first dose in neonates.

新生儿的首次剂量预测具有挑战性。在此概念验证研究中，我们的目标是进行从青少年小鼠到新生儿的药代动力学（PK）桥接研究，以研究被CYP3A代谢的药物。

我们选择了咪达唑仑和克林霉素作为模型药物。我们开发了使用NONMEM的少年小鼠群体PK模型。使用不同的校正方法，将这两种药物在幼年小鼠中的PK参数用于桥接新生儿的PK参数。通过0.5-1.5倍的折叠误差评估桥接结果。

具有和没有最大寿命潜力校正因子的简单异位测定法可分别用于从幼年小鼠到新生儿的清除率（CL）和分布体积（V _d）的桥接。模拟结果表明，对于咪达唑仑，100％的临床研究的预测CL和V _d均在观察值的0.5至1.5倍之内。对于克林霉素，临床研究的75％和100％的预测CL和V _d在观察值的0.5至1.5倍之内。

从幼年小鼠到新生儿，通过CYP3A代谢的药物之间的PK桥接是可行的。它可以作为ADE和PBPK模型的补充，以支持新生儿的首次剂量。