Gastrointestinal Parameters That Influence Oral Medications

Dressman, Jennifer B.; Bass, Paul; Ritschel, W. A.; Friend, David R.; Rubinstein, Abraham; Ziv, Ehud

doi:10.1002/jps.2600820902

Cited by 64 publications

(28 citation statements)

References 71 publications

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“…These various sections have been previously shown to have different rates for the transportmediated uptake of orally delivered compounds in the rat intestine (21,27). Furthermore, the bioavailability of both medicinal and nutritional compounds is dependent on the intestinal environment, where factors such as disease, pH, motility, and microflora can vary along the intestinal tract (9). As ABC transporters are highly involved in the transport of nutrients and drug compounds alike, we propose that expression patterns are a prerequisite to deciphering their functions in the gastrointestinal tract (GIT).…”

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confidence: 99%

Regional variations in ABC transporter expression along the mouse intestinal tract

Mutch

Anderle²,

Fiaux

et al. 2004

Physiological Genomics

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The ATP-binding cassette (ABC) family of proteins comprise a group of membrane transporters involved in the transport of a wide variety of compounds, such as xenobiotics, vitamins, lipids, amino acids, and carbohydrates. Determining their regional expression patterns along the intestinal tract will further characterize their transport functions in the gut. The mRNA expression levels of murine ABC transporters in the duodenum, jejunum, ileum, and colon were examined using the Affymetrix MuU74v2 GeneChip set. Eight ABC transporters (Abcb2, Abcb3, Abcb9, Abcc3, Abcc6, Abcd1, Abcg5, and Abcg8) displayed significant differential gene expression along the intestinal tract, as determined by two statistical models (a global error assessment model and a classic ANOVA, both with a P < 0.01). Concordance with semiquantitative real-time PCR was high. Analyzing the promoters of the differentially expressed ABC transporters did not identify common transcriptional motifs between family members or with other genes; however, the expression profile for Abcb9 was highly correlated with fibulin-1, and both genes share a common complex promoter model involving the NFκB, zinc binding protein factor (ZBPF), GC-box factors SP1/GC (SP1F), and early growth response factor (EGRF) transcription binding motifs. The cellular location of another of the differentially expressed ABC transporters, Abcc3, was examined by immunohistochemistry. Staining revealed that the protein is consistently expressed in the basolateral compartment of enterocytes along the anterior-posterior axis of the intestine. Furthermore, the intensity of the staining pattern is concordant with the expression profile. This agrees with previous findings in which the mRNA, protein, and transport function of Abcc3 were increased in the rat distal intestine. These data reveal regional differences in gene expression profiles along the intestinal tract and demonstrate that a complete understanding of intestinal ABC transporter function can only be achieved by examining the physiologically distinct regions of the gut.

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confidence: 99%

Regional variations in ABC transporter expression along the mouse intestinal tract

Mutch

Anderle²,

Fiaux

et al. 2004

Physiological Genomics

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“…It is influenced by a number of factors, including volume of ingested fluids, food type, fluid viscosity, drug action, physical characteristics of the solid dosage form, and biological factors such as age, posture, body mass index, physical activity, and certain diseases (36,63,64). A number of studies have stated that gastric emptying plays an important role in determining the retention time of dosage forms, even though it is highly variable (65)(66)(67). Under usual conditions, the gastric emptying time ranges from 5 min to 2 h. In general, the presence of food, especially fatty, reduces the gastric emptying time.…”

Section: Gastrointestinal Transitmentioning

confidence: 97%

Biomagnetic Methods: Technologies Applied to Pharmaceutical Research

et al. 2010

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Biomagnetic methods have been designed for a wide range of applications. Recently, such methods have been proposed as alternatives to scintigraphy for evaluating of a number of pharmaceutical processes in vitro as well as under the influence of gastrointestinal physiological parameters. In this review, physical characterization as well as the most recent applications of Superconducting Quantum Interference Device (SQUID), Anisotropic Magnetoresistive (AMR) and AC Biosusceptometry (ACB) in the pharmaceutical research will be explored. Moreover, their current status and how these technologies can be employed to improve the knowledge about the impact of gastrointestinal physiology on drug delivery in association with pharmacokinetic outcomes, termed pharmacomagnetography, will be presented.

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“…Caco-2 cells can have different permeability values compared to human intestine due to cacophilicity, which means a drug reversibly binds to Caco-2 and it results in underestimation of permeability values. Although pH of human intestine varies from acidic to slightly basic pH 65 , Caco-2 grows in fixed pH conditions. After cellbased permeability studies, sample analysis is mostly done using LC-MS tools.…”

Section: Challenges Associated With Cell Culture Modelsmentioning

confidence: 99%