Drug Absorption I: An In Situ Rat Gut Technique Yielding Realistic Absorption Rates

Doluisio, James T.; Billups, Norman F.; Dittert, Lewis W.; Sugita, Edwin T.; Swintosky, Joseph V.

doi:10.1002/jps.2600581006

Cited by 339 publications

(108 citation statements)

References 9 publications

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“…The Doluisio method entails use of an in situ rat gut technique for drug administration into the lumen (Doluisio et al, 1969;Sim and Back, 1988). In some rat preparations, the inflow and outflow of a select segment were monitored for drug disappearance, and arterial blood was sampled and the volume of blood was replenished by transfusion (Barr and Riegelman, 1970).…”

Section: Methods To Study Intestinal Transport and Metabolismmentioning

confidence: 99%

Modeling of Intestinal Drug Absorption: Roles of Transporters and Metabolic Enzymes (For the Gillette Review Series)

2003

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Section: Methods To Study Intestinal Transport and Metabolismmentioning

confidence: 99%

Modeling of Intestinal Drug Absorption: Roles of Transporters and Metabolic Enzymes (For the Gillette Review Series)

2003

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“…The in situ rat gut preparation described by Doluisio et al (1969) was used for the stomach and small intestine experiments. A similar technique was used to assess colonic absorption, in which a 15 cm segment of gut between the proximal (2 cm from its junction with the caecum) and distal colon (7 cm before the anus), was cannulated.…”

Section: Introduction Methodsmentioning

confidence: 99%

Gastric, intestinal and colonic absorption of metoprolol in the rat.

Domènech¹,

Alba²,

Morera³

et al. 1985

Brit J Clinical Pharma

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1The absorption of metoprolol from the stomach, small intestine and colon of anaesthetized rats has been evaluated using an in situ technique. Absorption rates were measured in terms of the rate of disappearance of metoprolol fumarate from the lumen between 5 and 30 min after dosing. Adsorption was estimated from the initial rapid fall in luminal content within the first 5 min after drug administration. 2 The rate of drug absorption from the stomach was low or negligible. In the small intestine, the absorption rate constants, ka, at pH 6.2 and 7.5 were 0.66 and 0.81 h-1, respectively. In the colon, the rate of drug absorption at pH 7.5 was faster (ka = 1.21 h-1) than in other segments of the gut. 3 Drug adsorption in the stomach amounted to 11% of the administered dose. In the small intestine adsorption was greater (16-22%), presumably because of the larger surface area in this segment of the gut, but in the colon adsorption was negligible.

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“…The in situ perfusion model allows for the measurement of drug permeability in the intact intestine by single-pass and recirculating methods (42)(43)(44) (Table III). For the single-pass (open loop) perfusion method, a section of intestine in an anesthetized animal is cannulated proximally and distally, rinsed with buffer solution, and then perfused with a drug solution.…”

Section: In Situ Perfusionmentioning

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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Drug Absorption I: An In Situ Rat Gut Technique Yielding Realistic Absorption Rates

Cited by 339 publications

References 9 publications

Modeling of Intestinal Drug Absorption: Roles of Transporters and Metabolic Enzymes (For the Gillette Review Series)

Modeling of Intestinal Drug Absorption: Roles of Transporters and Metabolic Enzymes (For the Gillette Review Series)

Gastric, intestinal and colonic absorption of metoprolol in the rat.

Application of Method Suitability for Drug Permeability Classification

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