We previously reported a prediction method for human pharmacokinetics (PK) using single species allometric scaling (SSS) and the complex Dedrick plot in chimeric mice with humanized liver to predict the total clearance (CL_t), distribution volumes in steady state (Vd_ss) and plasma concentration-time profiles of several drugs metabolized by cytochrome P450 (P450) and non-P450 enzymes. In the present study, we examined eight compounds (bosentan, cerivastatin, fluvastatin, pitavastatin, pravastatin, repaglinide, rosuvastatin, valsartan) as typical organic anion transporting polypeptide (OATP) substrates and six compounds metabolized by P450 and non-P450 enzymes to evaluate the predictability of CL_t, Vd_ss and plasma concentration-time profiles after intravenous administration to chimeric mice.

The predicted CL_t and Vd_ss of drugs that undergo OATP-mediated uptake and P450/non-P450-mediated metabolism reflected the observed data from humans within a three-fold error range.

We also examined the possibility of predicting plasma concentration-time profiles of drugs that undergo OATP-mediated uptake using the complex Dedrick plot in chimeric mice. Most profiles could be superimposed with observed profiles from humans within a two- to three-fold error range.

PK prediction using SSS and the complex Dedrick plot in chimeric mice can be useful for evaluating drugs that undergo both OATP-mediated uptake and P450/non-P450-mediated metabolism.

我们之前曾报道过一种预测人类药代动力学（PK）的方法，该方法使用单种异体缩放法（SSS）和具有人源化肝脏的嵌合小鼠的复杂Dedrick图来预测总清除率（CL _t），稳态下的分布量（Vd _ss）和被细胞色素P450（P450）和非P450酶代谢的几种药物的血浆浓度-时间曲线。在本研究中，我们检查了八种化合物（波生坦，西立伐他汀，氟伐他汀，匹伐他汀，普伐他汀，瑞格列奈，瑞舒伐他汀，缬沙坦）作为典型的有机阴离子转运多肽（OATP）底物，以及六种通过P450和非P450酶代谢的化合物来评估的CL预见性_吨，Vd的_SS 嵌合小鼠静脉给药后的血浆和血浆浓度-时间曲线。

预测的经历OATP介导的摄取和P450 /非P450介导的代谢的药物的CL _t和Vd _ss反映了人类在三倍误差范围内的观察数据。

我们还检查了在嵌合小鼠中使用复杂的Dedrick图预测接受OATP介导的药物的血浆浓度-时间曲线的可能性。大多数配置文件可以与人类观察到的配置文件重叠，误差范围为2到3倍。

在嵌合小鼠中使用SSS和复杂Dedrick图进行的PK预测可用于评估经历OATP介导的摄取和P450 /非P450介导的代谢的药物。