Absorption of Drugs from the Gastrointestinal Tract

Schanker, Lewis S.

doi:10.1007/978-3-642-65052-9_2

Cited by 44 publications

(42 citation statements)

References 20 publications

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“…The equilibrating flow for the stomach is only about 1/50 of the gastric mucosal flow of rats reported by Schanker, Shore, Brodie, and Hogben (19), estimating from the clearance of aniline from the blood into the lumen. However, these authors found values similar to those reported in the present paper when flow was calculated from the rate of D20 or salicylic acid clearance from the gastric lumen into the blood.…”

Section: Discussionmentioning

confidence: 75%

Use of Inert Gases to Study the Interaction of Blood Flow and Diffusion during Passive Absorption from the Gastrointestinal Tract of the Rat

Levitt

Levitt²

1973

J. Clin. Invest.

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A B S T R A C T Measurement of the relative absorption rates of inert gases (H2, He, CH4, SF6, and n33Xe) was used to investigate the interaction between diffusion and blood flow during passive absorption from the stomach, small bowel, and colon of the rat. If uptake is blood flow limited, the gases should be absorbed in proportion to their solubilities in blood, but if diffusion limited, uptake should be proportional to the diffusion rate of the gases in mucosal tissues.The observed absorption data were fitted to a series of models of interaction between perfusion and diffusion. A simple model accurately predicted the absorption rates of the gases from all segments of bowel. In this model, gas is absorbed into two distinct blood flows: one which flows in proximity to the lumen and completely equilibrates with the lumen, and a second which is sufficiently rapid and distant from the lumen that its gas uptake is entirely diffusion limited. The fraction of the total absorption attributable to the equilibrating flow can be readily calculated and equalled 93%, 77%, and 33% for the small bowel, colon, and stomach, respectively. Thus the rate of passive absorption of gases from the small bowel is limited almost entirely by the blood flow to the mucosa, and absorption from the stomach is largely limited by the diffusion rate of the gases. The flow which equilibrates with the lumen can be quantitated, and this flow may provide a useful measure of "effective" mucosal blood flow.

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Section: Discussionmentioning

confidence: 75%

Use of Inert Gases to Study the Interaction of Blood Flow and Diffusion during Passive Absorption from the Gastrointestinal Tract of the Rat

Levitt

Levitt²

1973

J. Clin. Invest.

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“…First mathematical models for i.v. (13), oral (14), and aerosol (15) modalities contributed to the development of those fields simulating drug uptake, distribution, metabolism, and elimination. The role of models is to interpret data mechanistically, predict outcomes, follow treatment courses, relate dose to response, establish safety criteria, design new drugs and delivery strategies, compare animal experiments to human applications, and tailor protocols to patient specific circumstances.…”

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confidence: 99%

Three-dimensional model of surfactant replacement therapy

Filoche

Tai

Grotberg

2015

Proc. Natl. Acad. Sci. U.S.A.

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Surfactant replacement therapy (SRT) involves instillation of a liquid-surfactant mixture directly into the lung airway tree. It is widely successful for treating surfactant deficiency in premature neonates who develop neonatal respiratory distress syndrome (NRDS). However, when applied to adults with acute respiratory distress syndrome (ARDS), early successes were followed by failures. This unexpected and puzzling situation is a vexing issue in the pulmonary community. A pressing question is whether the instilled surfactant mixture actually reaches the adult alveoli/acinus in therapeutic amounts. In this study, to our knowledge, we present the first mathematical model of SRT in a 3D lung structure to provide insight into answering this and other questions. The delivery is computed from fluid mechanical principals for 3D models of the lung airway tree for neonates and adults. A liquid plug propagates through the tree from forced inspiration. In two separate modeling steps, the plug deposits a coating film on the airway wall and then splits unevenly at the bifurcation due to gravity. The model generates 3D images of the resulting acinar distribution and calculates two global indexes, efficiency and homogeneity. Simulating published procedural methods, we show the neonatal lung is a well-mixed compartment, whereas the adult lung is not. The earlier, successful adult SRT studies show comparatively good index values implying adequate delivery. The later, failed studies used different protocols resulting in very low values of both indexes, consistent with inadequate acinar delivery. Reasons for these differences and the evolution of failure from success are outlined and potential remedies discussed.surfactant replacement therapy | pulmonary drug delivery | biological fluid mechanics | respiratory distress syndrome | biological transport processes S ince the early 1980s, surfactant replacement therapy (SRT) has been successful in applications to prematurely born neonates to treat their lack of surfactant production, which normally initiates late in gestation (1). Because surfactant reduces the surface tension between the air and the lung's liquid lining, its deficiency creates high surface tensions and collapsed, stiff lungs making them difficult to inflate. The resulting clinical entity of labored breathing and poor oxygenation is called neonatal respiratory distress syndrome (NRDS), or hyaline membrane disease, and is a risk of premature birth increasing with decreasing gestational age. The incidence is ∼1% of all births, equating to 40,000 cases annually in the United States (2). The mortality associated with NRDS dropped from 4,997 deaths in 1980 to 861 in 2005, and SRT played an important role in this success (3).SRT has also been tried in adults whose surfactant systems are compromised by acute respiratory distress syndrome (ARDS). ARDS results from overwhelming infections, mechanical injuries, and other insults either directly or indirectly to the lung. ARDS cases in the United States total 190,600 annually wit...

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“…The absorption experiments were performed in cecum using an in-situ closed loop method (18,19). Initial concentration of 9-AC was 72.9 μM.…”

Section: Determination Of Absorption Rate Constantmentioning

confidence: 99%

“…A closed loop method was used in the in-situ cecum absorption study to estimate the availability of 9-AC through the cecum and liver (F c,h ) after absorption from the cecum (18,19,21). The blood samples were collected from the right femoral artery after 72.9 μM of 9-AC in 4 ml of isotonic phosphate-buffered solution (pH 6.8) was administrated into the rat cecum.…”

Section: In-situ Cecum Absorption Studymentioning

confidence: 99%

Pharmacokinetic Modeling of Absorption Behavior of 9-Aminocamptothecin (9-AC) Released from Colon-specific HPMA Copolymer–9-AC Conjugate in Rats

et al. 2007

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Purpose-To quantitate and predict colon-specific 9-aminocamptothecin (9-AC) release from the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-9-AC conjugate and its absorption behavior after oral administration in rats.Methods-Drug distribution in the gastrointestinal (GI) tract and the plasma concentration-time profile of 9-AC released from the HPMA copolymer conjugate were predicted using the degradation, transit, and absorption rate constants in cecum. The fate of 9-AC in cecum and liver was measured by in-situ cecum absorption and liver perfusion.Results-Following oral administration of the conjugate, 9-AC was released rapidly in cecum. Based on the pharmacokinetic model, up to 60% of the dose was in the cecum at ∼6 h, and 7% of the dose still remained there at 24 h. The predicted plasma concentration curve for released 9-AC after an oral dose of 3 mg/kg of 9-AC equivalent increased gradually and reached a peak of 98 nM at 7 h, then started decreasing slowly to 16 nM at 24 h. The bioavailability value was estimated as 0.31 after the first-pass elimination.Conclusions-A pharmacokinetic model delineated the impact of GI transit, drug absorption rate, and first-pass metabolism on drug disposition following oral administration of HPMA copolymer-9-AC conjugate in rats.

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Absorption of Drugs from the Gastrointestinal Tract

Cited by 44 publications

References 20 publications

Use of Inert Gases to Study the Interaction of Blood Flow and Diffusion during Passive Absorption from the Gastrointestinal Tract of the Rat

Use of Inert Gases to Study the Interaction of Blood Flow and Diffusion during Passive Absorption from the Gastrointestinal Tract of the Rat

Three-dimensional model of surfactant replacement therapy

Pharmacokinetic Modeling of Absorption Behavior of 9-Aminocamptothecin (9-AC) Released from Colon-specific HPMA Copolymer–9-AC Conjugate in Rats

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