QSAR-based permeability model for drug-like compounds

Gozalbes, Rafael; Jacewicz, Mary; Annand, Robert R.; Tsaioun, Katya; Pineda‐Lucena, Antonio

doi:10.1016/j.bmc.2011.03.011

Cited by 48 publications

(39 citation statements)

References 28 publications

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“…Therefore, the experimental Caco-2 permeability value for amlodipine should be considered as approximate. Caco-2 permeability values for amlodipine are in agreement with BCS Class I classification for these drugs and their known high bioavailability in humans [10][11][12][13].…”

Section: Resultssupporting

confidence: 68%

Quantitative Determination of Amlodipine From Caco-2 Cell Monolayers by High-Performance Liquid Chromatography–mass Spectrometry/Mass Spectrometry

Logoyda

2018

Asian J Pharm Clin Res

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Objective: A simple, rapid high-performance liquid chromatography-mass spectrometry/mass spectrometry (MS/MS) method was developed for the determination of amlodipine from confluent Caco-2 monolayers and from aqueous solution. . The initial content of the eluent B is 0%, which increases linearly by 1.0 min to 100% and to 1.01 min returns to the initial 0%. The mobile phase was delivered at a flow rate of 0.400 ml/min into the MS electrospray ionization chamber. The sample volume was 5 µl.Results: Under these conditions, amlodipine was eluted at 1.61 min. According to the Caco-2 test results, amlodipine appeared to have moderate to high permeability. Recovery value for amlodipine is 52.33%. Caco-2 permeability values for amlodipine are in agreement with BCS Class I classification for these drugs and their known high bioavailability in humans. Conclusion:A new rapid method was developed for the determination of amlodipine from confluent Caco-2 monolayers and from aqueous solution. Acquired results demonstrate that proposed strategy can be effortlessly and advantageously applied for the examination of amlodipine from Caco-2 cell monolayers.

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Section: Resultssupporting

confidence: 68%

Quantitative Determination of Amlodipine From Caco-2 Cell Monolayers by High-Performance Liquid Chromatography–mass Spectrometry/Mass Spectrometry

Logoyda

2018

Asian J Pharm Clin Res

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“…Permeability values for CaCo-2 cells were taken from 58 , except for fenoprofen 59 , phenacetin 60 , and linezolid and prednisolone 61 . Permeability values of MDR1-MDCK cells for pindolol and timolol were derived from 62 and for quinidine from 63 .…”

Section: Methodsmentioning

confidence: 99%

Multi-functional scaling methodology for translational pharmacokinetic and pharmacodynamic applications using integrated microphysiological systems (MPS)

Maaß

Stokes²,

Griffith

et al. 2017

Integr. Biol.

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Microphysiological systems (MPS) provide relevant physiological environments in vitro for studies of pharmacokinetics, pharmacodynamics and biological mechanisms for translational research. Designing multi-MPS platforms is essential to study multi-organ systems. Typical design approaches, including direct and allometric scaling, scale each MPS individually and are based on relative sizes not function. This study’s aim was to develop a new multi-functional scaling approach for integrated multi-MPS platform design for specific applications. We developed an optimization approach using mechanistic modeling and specification of an objective that considered multiple MPS functions, e.g., drug absorption and metabolism, simultaneously to identify system design parameters. This approach informed the design of two hypothetical multi-MPS platforms consisting of gut and liver (multi-MPS platform I) and gut, liver and kidney (multi-MPS platform II) to recapitulate in vivo drug exposures in vitro. This allows establishment of clinically relevant drug exposure-response relationships, a prerequisite for efficacy and toxicology assessment. Design parameters resulting from multi-functional scaling were compared to designs based on direct and allometric scaling. Human plasma time-concentration profiles of eight drugs were used to inform the designs, and profiles of an additional five drugs were calculated to test the designed platforms on an independent set. Multi-functional scaling yielded exposure times in good agreement with in vivo data, while direct and allometric scaling approaches resulted in short exposure durations. Multi-functional scaling allows appropriate scaling from in vivo to in vitro of multi-MPS platforms, and in the cases studied provides designs that better mimic in vivo exposures than standard MPS scaling methods.

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“…We have explored the performance of several methods from the literature [30–34]; the results are presented in Table 3. Each of the methods employ a small number of molecular and topological descriptors; in some cases only a single descriptor has been used (for example, the topological surface area [32] or polar surface area [33]) while other methods use a combination of them (polar surface area and molecular weight [30] or hydrogen bond-related properties and the octanol-water partition coefficient [31]).…”

Section: Resultsmentioning

confidence: 99%

BioPPSy: An Open-Source Platform for QSAR/QSPR Analysis

et al. 2016

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The reliability of quantitative structure-property relationship (QSPR) and quantitative structure-activity relationship (QSAR) models is often difficult to assess due to the problems of accessing the tools and data used to build the models. We present here BioPPSy, which aims to fill this gap by providing an easy-to-use open-source software platform. We demonstrate the program capabilities by calculating three key properties used in drug discovery, aqueous solubility, Caco-2 cell permeability and blood-brain barrier permeability. A comparison is made with a number of previously reported methods, taken from the literature, for each property. The software, including source code, current models and databases, is available from https://sourceforge.net/projects/bioppsy/.

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QSAR-based permeability model for drug-like compounds

Cited by 48 publications

References 28 publications

Quantitative Determination of Amlodipine From Caco-2 Cell Monolayers by High-Performance Liquid Chromatography–mass Spectrometry/Mass Spectrometry

Quantitative Determination of Amlodipine From Caco-2 Cell Monolayers by High-Performance Liquid Chromatography–mass Spectrometry/Mass Spectrometry

Multi-functional scaling methodology for translational pharmacokinetic and pharmacodynamic applications using integrated microphysiological systems (MPS)

BioPPSy: An Open-Source Platform for QSAR/QSPR Analysis

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