Abstract：
(1) Background: this article investigates which PK metrics in a single-dose study (concentration at the end of posology interval, Cτ, partial areas under the curve, pAUCs, or half-value duration, HVD) are more sensitive and less variable for predicting the failure of a prolonged-release product at steady-state that was the bioequivalent for Cmax, AUC0-t and AUC0-inf, in the single-dose study; (2) Methods: a cross-over study was performed in 36 subjects receiving desvenlafaxine 100 mg prolonged-release tablets. Conventional (Cmax, AUC0-t and AUC0-inf) and additional (Cτ, pAUCs and HVD) PK metrics were considered after single-dose conditions. Predicted PK metrics at steady state (AUC0-τ, Cmax,ss, and Cτ,ss) were derived using a population PK model approach; (3) Results: the existing differences in the shape of the concentration-time curves precluded to show equivalence for Cτ,ss in the simulated study at steady state. This failure to show equivalence at steady state was predicted by Cτ, pAUCs and HVD in the single-dose study. Cτ was the most sensitive metric for detecting the different shape, with a lower intra-subject variability than HVD; (4) Conclusions: conventional PK metrics for single-dose studies (Cmax, AUC0-t and AUC0-inf) are not enough to guarantee bioequivalence at steady state for prolonged-release products.
摘要：
（1）背景：本文调查了单剂量研究中的哪些PK指标（姿势间隔结束时的浓度，Cτ,曲线下的部分区域，pAUCs,或半值持续时间，HVD）对于预测长期释放产品在稳态下的失效更敏感且变量更小，这是Cmax的生物等效性，AUC0-t和AUC0-inf，在单剂量研究中；（2）方法：在接受去文拉法辛100mg缓释片的36名受试者中进行了一项交叉研究。常规(Cmax，AUC0-t和AUC0-inf)和附加(Cτ，单剂量条件后考虑pAUC和HVD)PK指标。稳态下的预测PK指标(AUC0-τ，Cmax,ss,和Cτ，ss）是使用种群PK模型方法得出的；（3）结果：浓度-时间曲线形状的现有差异排除了对Cτ的等效性，SS在稳态下的模拟研究中。Cτ预测了在稳态下未能显示等效性，单剂量研究中的pAUCs和HVD。Cτ是检测不同形状的最敏感指标，受试者内变异性低于HVD；(4)结论：单剂量研究的常规PK指标(Cmax，AUC0-t和AUC0-inf）不足以保证长期释放产品在稳态下的生物等效性。
