Prediction of the in vitro permeability determined in Caco-2 cells by using artificial neural networks

Paixão, Paulo; Gouveia, Luís F.; Morais, José

doi:10.1016/j.ejps.2010.05.014

Cited by 54 publications

(29 citation statements)

References 104 publications

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“…The AUC values for fluconazole by the intravenous and oral routes have been found to be similar and more than 90% drug is absorbed after oral administration . Data from Caco‐2 permeability studies confirm the classification of fluconazole as highly permeable …”

Section: Discussionmentioning

confidence: 64%

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Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Fluconazole

Charoo¹,

Cristofoletti²,

Graham³

et al. 2014

Journal of Pharmaceutical Sciences

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Section: Discussionmentioning

confidence: 64%

“…An in vitro log P app (cm/s) value of –4.82 is also reported . Experimental conditions were not provided in the reference.…”

Section: Pharmacokinetic Propertiesmentioning

confidence: 99%

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Fluconazole

Charoo¹,

Cristofoletti²,

Graham³

et al. 2014

Journal of Pharmaceutical Sciences

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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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“…Using a slightly larger training set of Caco‐2 permeability, Paixão et al. used artificial neural networks to model the data 12. Similar to the Castillo‐Garit paper, a table is included in the article summarizing prior permeability models and pointing out the rather small average training set size ( n =7 to 106) resulting in R 2 values ranging from 0.16 to 0.74.…”

Section: Introductionmentioning

confidence: 99%