Combined Application of Parallel Artificial Membrane Permeability Assay and Caco-2 Permeability Assays in Drug Discovery

Kerns, Edward H.; Di, Li; Petusky, Susan; Farris, Michele; Ley, Rob; Jupp, Phil

doi:10.1002/jps.20075

Cited by 244 publications

(162 citation statements)

References 31 publications

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“…The verapamil permeability described in the literature is about 14.0 (10 −6 cm/s) (28,29); meanwhile, the experimental permeability determined in our studies was 11.5±3.21 (10 −6 cm/s), so it can be assumed that the conditions of the PAMPA experiment are correct. The five compounds studied are shown in Fig.…”

Section: Gastrointestinal Permeability Studies (Pampa)supporting

confidence: 47%

“…The extent of permeation through the membrane is measured and compared with a known degree of drug absorption in humans. An excellent correlation was demonstrated between the flux across PAMPA systems and the extent of absorption of a diverse set of well-characterized drugs in humans (16)(17)(18)(19)(20)(21). No good correlation is observed when the drug is transported by active transport mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Membrane Permeability (PAMPA and Skin) of Benzimidazoles with Potential Cannabinoid Activity and their Relation with the Biopharmaceutics Classification System (BCS)

et al. 2011

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Abstract. The permeability of five benzimidazole derivates with potential cannabinoid activity was determined in two models of membranes, parallel artificial membrane permeability assay (PAMPA) and skin, in order to study the relationship of the physicochemical properties of the molecules and characteristics of the membranes with the permeability defined by the Biopharmaceutics Classification System. It was established that the PAMPA intestinal absorption method is a good predictor for classifying these molecules as very permeable, independent of their thermodynamic solubility, if and only if these have a Log P oct value <3.0. In contrast, transdermal permeability is conditioned on the solubility of the molecule so that it can only serve as a model for classifying the permeability of molecules that possess high solubility (class I: high solubility, high permeability; class III: high solubility, low permeability).

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Section: Gastrointestinal Permeability Studies (Pampa)supporting

confidence: 47%

Section: Introductionmentioning

confidence: 99%

Evaluation of the Membrane Permeability (PAMPA and Skin) of Benzimidazoles with Potential Cannabinoid Activity and their Relation with the Biopharmaceutics Classification System (BCS)

et al. 2011

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“…After the incubation time, the ratio of compound which has crossed the artificial membrane is calculated and used to obtain the effective passive permeability value P e (cm/s), which is a constant value for each compound tested (see Material and Methods for details on the equations). Such an evaluation of the physicochemical properties of a compound of interest is thus very advantageous for the early prediction of its passive absorption because several correlations have been reported in the literature between P e values and in vitro or in vivo absorption data [12,15,17,18]. The popularity of PAMPA has rapidly risen in the industry as a versatile and cost-effective assay compared to standard cellular models such as Caco-2 [19,20].…”

mentioning

confidence: 99%

Prediction of the Passive Intestinal Absorption of Medicinal Plant Extract Constituents with the Parallel Artificial Membrane Permeability Assay (PAMPA)

et al. 2016

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At the early drug discovery stage, the high-throughput parallel artificial membrane permeability assay is one of the most frequently used in vitro models to predict transcellular passive absorption. While thousands of new chemical entities have been screened with the parallel artificial membrane permeability assay, in general, permeation properties of natural products have been scarcely evaluated. In this study, the parallel artificial membrane permeability assay through a hexadecane membrane was used to predict the passive intestinal absorption of a representative set of frequently occurring natural products. Since natural products are usually ingested for medicinal use as components of complex extracts in traditional herbal preparations or as phytopharmaceuticals, the applicability of such an assay to study the constituents directly in medicinal crude plant extracts was further investigated. Three representative crude plant extracts with different natural product compositions were chosen for this study. The first extract was composed of furanocoumarins (Angelica archangelica), the second extract included alkaloids (Waltheria indica), and the third extract contained flavonoid glycosides (Pueraria montana var. lobata). For each medicinal plant, the effective passive permeability values Pe (cm/s) of the main natural products of interest were rapidly calculated thanks to a generic ultrahigh-pressure liquid chromatography-UV detection method and because Pe calculations do not require knowing precisely the concentration of each natural product within the extracts. The original parallel artificial membrane permeability assay through a hexadecane membrane was found to keep its predictive power when applied to constituents directly in crude plant extracts provided that higher quantities of the extract were initially loaded in the assay in order to ensure suitable detection of the individual constituents of the extracts. Such an approach is thus valuable for the high-throughput, cost-effective, and early evaluation of passive intestinal absorption of active principles in medicinal plants. In phytochemical studies, obtaining effective passive permeability values of pharmacologically active natural products is important to predict if natural products showing interesting activities in vitro may have a chance to reach their target in vivo.

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“…We can deduce that N-alkylation of uracil with both hydroxyethyl and acetoxyethyl substituents gave target N-1-MOM uracil derivatives in rather low yield (~20 %). Thus, we applied a more efficient N-methoxymethylation using same reaction conditions but starting from 2,4-dimethoxy-5-(2-hydroxyethyl)uracil (8) to give N-1-MOM (15) in improved yield of 46 %. Compounds 16 and 17 with 2-(methoxymethoxy)ethyl substituent at C-5 were also isolated as byproducts.…”

Section: Bioorganic and Medicinal Chemistry Lettersmentioning

confidence: 99%

“…Permeability assay was designed to determine permeability of selected compounds through MDCKII-MDR1 cell monolayers, as well as for their identification as potential P-gp supstrate. 15 MDCKII-MDR1 cells are Madin-Darby canine kidney cells with overexpressed MDR1 (human multidrug resistance 1) gene. This gene encodes an integral membrane protein P-gp that functions as ATP-dependant efflux pump, which could have a significant influence on compounds permeability.…”

Section: Bioorganic and Medicinal Chemistry Lettersmentioning

confidence: 99%

Synthesis, cytostatic activity and ADME properties of C-5 substituted and N-acyclic pyrimidine derivatives

Kraljević

Klika

Kralj

et al. 2012

Bioorganic & Medicinal Chemistry Letters

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Combined Application of Parallel Artificial Membrane Permeability Assay and Caco-2 Permeability Assays in Drug Discovery

Cited by 244 publications

References 31 publications

Evaluation of the Membrane Permeability (PAMPA and Skin) of Benzimidazoles with Potential Cannabinoid Activity and their Relation with the Biopharmaceutics Classification System (BCS)

Evaluation of the Membrane Permeability (PAMPA and Skin) of Benzimidazoles with Potential Cannabinoid Activity and their Relation with the Biopharmaceutics Classification System (BCS)

Prediction of the Passive Intestinal Absorption of Medicinal Plant Extract Constituents with the Parallel Artificial Membrane Permeability Assay (PAMPA)

Synthesis, cytostatic activity and ADME properties of C-5 substituted and N-acyclic pyrimidine derivatives

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