<i>In vitro</i> systems for studying intestinal drug absorption

Hillgren, Kathleen M.; Kato, Akira; Borchardt, Ronald T.

doi:10.1002/med.2610150202

Cited by 172 publications

(85 citation statements)

References 171 publications

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“…The absorption parameters of berberine in the three intestinal segments (duodenum, jejunum, ileum) were tested by in vitro method as described (14,16). In vitro permeation studies were performed using everted small intestine segments.…”

Section: Preparation Of the Everted Rat Gut Sacsmentioning

confidence: 99%

Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine

Zhang

et al. 2010

AAPS PharmSciTech

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Abstract. Berberine, a plant alkaloid used in traditional Chinese medicine, has a wide spectrum of pharmacological actions, but the poor bioavailability limits its clinical use. The present aim was to observe the effects of sodium caprate on the intestinal absorption and antidiabetic action of berberine. The in situ, in vitro, and in vivo models were used to observe the effect of sodium caprate on the intestinal absorption of berberine. Intestinal mucosa morphology was measured to evaluate the toxic effect of sodium caprate. Diabetic model was used to evaluate antidiabetic effect of berberine coadministrated with sodium caprate. The results showed that the absorption of berberine in the small intestine was poor and that sodium caprate could significantly improve the poor absorption of berberine in the small intestine. Sodium caprate stimulated mucosal-to-serosal transport of berberine; the enhancement ratios were 2.08, 1.49, and 3.49 in the duodenum, jejunum, and ileum, respectively. After coadministration, the area under the plasma concentration-time curve of berberine was increased 28% than that in the absence of sodium caprate. Furthermore, both berberine and coadministration with sodium caprate orally could significantly decrease fasting blood glucose and improve glucose tolerance in diabetic rats (P<0.05). The hypoglycemic effect of coadministration group was remarkably stronger, and the areas under the glucose curves was decreased 22.5%, compared with berberine treatment group (P< 0.05). Morphologic analysis indicated that sodium caprate was not significantly injurious to the intestinal mucosa. The study demonstrates that sodium caprate could significantly promote the absorption of berberine in intestine and enhance its antidiabetic effect without any serious mucosal damage.

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Section: Preparation Of the Everted Rat Gut Sacsmentioning

confidence: 99%

Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine

Zhang

et al. 2010

AAPS PharmSciTech

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“…Lead transport across the intestinal epithelium that is independent of lead speciation, e.g., via processes such as pinocytosis, is considered negligible (Hillgren et al 1995). Therefore, lead speciation can be assumed to influence the availability of lead for transport across the intestinal epithelium.…”

Section: Availability For Transport Across the Intestinal Epitheliummentioning

confidence: 99%

Lead Speciation in Artificial Human Digestive Fluid

Oomen

Tolls

Sips

et al. 2003

Archives of Environmental Contamination and Toxicology

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Abstract. For children, soil ingestion via hand-to-mouth behavior can be a main route of exposure to contaminants such as lead. The ingested lead can be mobilized from the soil and form new species during the digestion process. Speciation is known to affect the availability of metals for transport across biological membranes. In the present study, in vitro digestions were performed with (artificially contaminated) standard soil. Lead speciation was investigated in the artificial human intestinal fluid, i.e., chyme, to gain insight into the lead species and lead fractions that may be available for transport across the intestinal epithelium. To that end, both a lead ion selective electrode (Pb-ISE) and a voltammetric technique (differential pulse anodic stripping voltammetry, DPASV) were used. The results indicate that in chyme only a negligible lead fraction is present as free Pb 2ϩ , whereas lead phosphate and lead bile complexes are important fractions. The lead phosphate complexes appear to be voltammetrically labile, i.e., in dynamic equilibrium with Pb 2ϩ . Labile complexes can dissociate and the produced metal ions can subsequently be transported across the intestinal epithelium. Lead bile complexes may behave in a similar manner, or this organometal complex may be able to traverse the intestinal membrane. Therefore, substantially more than only the free metal ion should be considered available for transport across the intestinal epithelium.

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“…Experimental conditions need to be first optimized and controlled for the physiological environment that drugs encounter in the intestinal tract to obtain satisfactory in vitro-in vivo correlations (IVIVC) (8)(9)(10)(11)(12). To make the models useful in drug discovery and development, there is a need to establish a correlation between experimental and in vivo absorption with standardized methods for the quantification of permeability data (9,13).…”

Section: Introductionmentioning

confidence: 99%

Application of Method Suitability for Drug Permeability Classification

Volpe

2010

AAPS J

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Abstract. Experimental models of permeability in animals, excised tissues, cell monolayers, and artificial membranes are important during drug discovery and development as permeability is one of several factors affecting the intestinal absorption of oral drug products. The utility of these models is demonstrated by their ability to predict a drug's in vivo intestinal absorption. Within the various permeability models, there are differences in the performance of the assays, along with variability in animal species, tissue sources, and cell types, resulting in a variety of experimental permeability values for the same drug among laboratories. This has led to a need for assay standardization within laboratories to ensure applicability in the drug development process. Method suitability provides a generalized approach to standardize and validate a permeability model within a laboratory. First, assay methodology is optimized and validated for its various experimental parameters along with acceptance criteria for the assay. Second, the suitability of the model is demonstrated by a rank order relationship between experimental permeability values and human extent of absorption of known model compounds. Lastly, standard compounds are employed to classify a test drug's intestinal permeability and ensure assay reproducibility and quality. This review will provide examples of the different aspects method suitability for in situ (intestinal perfusions), ex vivo (everted intestinal sacs, diffusion chambers), and in vitro (cell monolayers, artificial membranes) experimental permeability models. Through assay standardization, reference standards, and acceptance criteria, method suitability assures the dependability of experimental data to predict a drug's intestinal permeability during discovery, development, and regulatory application.KEY WORDS: artificial membranes; drug permeability; ex vivo perfusion; in situ perfusion; in vitro cell monolayers; method suitability.

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In vitro systems for studying intestinal drug absorption

Cited by 172 publications

References 171 publications

Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine

Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine

Lead Speciation in Artificial Human Digestive Fluid

Application of Method Suitability for Drug Permeability Classification

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