局部乳膏制剂生物等效性评估的新方法：胶带剥离数据的基于模型的分析正确地得出BE和BIE,Pharmaceutical Research

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局部乳膏制剂生物等效性评估的新方法：胶带剥离数据的基于模型的分析正确地得出BE和BIE
Pharmaceutical Research ( IF 3.5 ) Pub Date : 2020-01-02 , DOI: 10.1007/s11095-019-2724-2
Deniz Ozdin _{1,

2} , Isadore Kanfer _{3,

4} , Murray P Ducharme _{1,

2}

Affiliation

目的

这项研究的目的是（a）提出一种新颖的皮肤药代动力学（DPK）方法，从中可以推导出与局部用药的生物等效性（BE）评估有关的药代动力学参数，同时避免了对大量测量和假设的需求，并且（b ）以调查此方法是否能够正确确定BE和生物不等价（BIE）。

方法

将阿昔洛韦的生物等效和生物等效制剂与参考产品进行比较。在吸收阶段中仅以一个剂量持续时间进行胶带剥离，以产生角质层与时间的关系曲线中的药物含量，每个时间点对应一个剥离层。使用非线性混合效应模型（ADAPT5®）（MLEM算法）拟合DPK数据，并估计药物吸收/输入皮肤的速率（K _in）和程度（F _S）。使用平均BE方法评估结果。

结果

估计接触度量是用于生物等效制剂的通常BE限度内（F_小号：102.4 [90％CI：97.5-107.7]; k_中：94.2 [90％CI：83.7-106.0]），但这些限制为bioinequivalent外制剂（F_小号：43.4 [90％CI：27.9-67.6]; k_中：54.5 [90％CI：36.6-81.1]）。

结论

所提出的新颖的DPK方法被证明是成功的，健壮的并且可用于局部制剂之间正确评估BE和BIE。

"点击查看英文标题和摘要"

Novel Approach for the Bioequivalence Assessment of Topical Cream Formulations: Model-Based Analysis of Tape Stripping Data Correctly Concludes BE and BIE

Purpose

The purpose of this study was (a) to suggest a novel dermatopharmacokinetic (DPK) approach from which pharmacokinetic parameters relevant to the bioequivalence (BE) assessment of a topical formulation can be deduced while circumventing the need for numerous measurements and assumptions, and (b) to investigate whether this approach enables the correct conclusion of BE and bioinequivalence (BIE).

Methods

Bioequivalent and bioinequivalent formulations of acyclovir were compared versus a reference product (Zovirax®). Tape Stripping was conducted at only one dose duration during the uptake phase to generate drug content in stratum corneum versus time profiles, each time point corresponding to one stripped layer. Nonlinear mixed effect modeling (ADAPT5®) (MLEM algorithm) was used to fit the DPK data and to estimate the rate (K_in) and extent (F_S) of drug absorption/input into the skin. Results were evaluated using the average BE approach.

Results

Estimated exposure metrics were within the usual BE limits for the bioequivalent formulation (F_S: 102.4 [90%CI: 97.5–107.7]; K_in: 94.2 [90%CI: 83.7–106.0]), but outside those limits for the bioinequivalent formulation (F_S: 43.4 [90%CI: 27.9–67.6]; K_in: 54.5 [90%CI: 36.6–81.1]).