Application of the Finite Absorption Time (F.A.T.) Concept in the Assessment of Bioequivalence.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2024-07-01 Epub Date: 2024-06-19 DOI:10.1007/s11095-024-03727-w

Athanasios A Tsekouras, Panos Macheras

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引用次数: 0

Abstract

Purpose: Το formulate a methodology for the assessment of bioequivalence using metrics, which are based on the physiologically sound F.A.T.

Concept:

Methods: The equations of the physiologically based finite time pharmacokinetic models for the one-and two-compartment model with one and two input stages of absorption were solved to derive metrics for the extent and rate of absorption. Simulated data were used to study the proper way for the estimation of metrics. A bioequivalence study was analyzed using these metrics.

Results: The rate of drug absorption was found to be equal to the slope of the amount absorbed versus time curve. The amount of drug absorbed at the end of the absorption process, corresponding to the blood concentration at F.A.T. is an indicator of the extent of absorption. The plot of the ratio test/reference of the simulated data for the amount absorbed as a function of time becomes constant beyond the end of drug absorption from the formulation exhibiting the longer absorption. The assessment of the bioequivalence study was based on the slope of the amount absorbed versus time curve for the rate of absorption, while the estimate for the constant ratio test/reference for the amount absorbed was used for the assessment of extent of absorption.

Conclusions: The assessment of rate in bioequivalence studies can be based on the estimation of slope of the percent absorbed versus time curve while the constant ratio test/reference for the amount of drug absorbed is an indicator of the extent of absorption.

Abstract Image

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有限吸收时间 (F.A.T.) 概念在生物等效性评估中的应用。

目的：Το 根据生理学上合理的 F.A.T.概念，制定使用指标评估生物等效性的方法：方法：对具有一个和两个吸收输入阶段的一室和二室模型的生理学有限时间药代动力学模型方程进行求解，得出吸收范围和吸收速率的指标。模拟数据用于研究估算指标的正确方法。使用这些指标对生物等效性研究进行了分析：结果：发现药物吸收率等于吸收量与时间曲线的斜率。吸收过程结束时的药物吸收量（相当于 F.A.T. 时的血液浓度）是药物吸收程度的指标。吸收量随时间变化的试验/参考模拟数据比值图在吸收时间较长的制剂药物吸收结束后变得恒定。生物等效性研究的评估基于吸收率的吸收量随时间变化曲线的斜率，而吸收程度的评估则使用吸收量的恒定比率测试/参考值的估计值：结论：生物等效性研究中的吸收率评估可基于吸收百分比与时间曲线斜率的估算，而吸收药物量的恒定比试验/参考值则是吸收程度的指标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.