Evaluation of the Intelisite capsule to deliver theophylline and frusemide tablets to the small intestine and colon

Clear, Nicola; Milton, Ashley; Humphrey, Michael; Henry, Brian; Wulff, Maria; Nichols, D. J.; Anziano, Richard J.; Wilding, Ian R.

doi:10.1016/s0928-0987(01)00134-8

Cited by 47 publications

(21 citation statements)

References 20 publications

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“…Furosemide strongly binds to plasma proteins (91-99%) (34), particularly to anionic sites on albumin (20). Most intestinal furosemide absorption occurs in the stomach and small intestine (30,58,160). Although the mean availability of oral furosemide is ϳ60%, absorption ranges from 10 -100%.…”

Section: Pharmacology Pharmacodynamics Pharmacokinetics Of Furosemidementioning

confidence: 99%

Everything we always wanted to know about furosemide but were afraid to ask

Huang

Mees

Vos

et al. 2016

American Journal of Physiology-Renal Physiology

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Huang X, Dorhout Mees E, Vos P, Hamza S, Braam B. Everything we always wanted to know about furosemide but were afraid to ask. Am J Physiol Renal Physiol 310: F958 -F971, 2016. First published February 24, 2016 doi:10.1152/ajprenal.00476.2015.-Furosemide is a widely used, potent natriuretic drug, which inhibits the Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC)-2 in the ascending limb of the loop of Henle applied to reduce extracellular fluid volume expansion in heart and kidney disease. Undesirable consequences of furosemide, such as worsening of kidney function and unpredictable effects on sodium balance, led to this critical evaluation of how inhibition of NKCC affects renal and cardiovascular physiology. This evaluation reveals important knowledge gaps, involving furosemide as a drug, the function of NKCC2 (and NKCC1), and renal and systemic indirect effects of NKCC inhibition. Regarding renal effects, renal blood flow and glomerular filtration rate could become compromised by activation of tubuloglomerular feedback or by renin release, particularly if renal function is already compromised. Modulation of the intrarenal renin angiotensin system, however, is ill-defined. Regarding systemic effects, vasodilation followed by nonspecific NKCC inhibition and changes in venous compliance are not well understood. Repetitive administration of furosemide induces short-term (braking phenomenon, acute diuretic resistance) and long-term (chronic diuretic resistance) adaptations, of which the mechanisms are not well known. Modulation of NKCC2 expression and activity in kidney and heart failure is ill-defined. Lastly, furosemide's effects on cutaneous sodium stores and on uric acid levels could be beneficial or detrimental. Concluding, a considerable knowledge gap is identified regarding a potent drug with a relatively specific renal target, NKCC2, and renal and systemic actions. Resolving these questions would increase the understanding of NKCCs and their actions and improve rational use of furosemide in pathophysiology of fluid volume expansion. extracellular fluid volume; natriuresis; renal function; chronic kidney disease; heart failure DIURETICS BLOCKING THE Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC) have an important place in the treatment of fluid overload, specifically in the context of kidney disease and heart failure (64). Of the drugs that inhibit the NKCC2 in the loop of Henle (furosemide, bumetanide, torsemide, ethacrynic acid), furosemide is most commonly applied (66) and Ͼ40 million prescriptions are dispensed every year in the USA (66a). However, many uncertainties remain about intrarenal and systemic actions of furosemide, including its two main targets NKCC1 and NKCC2.Clinically, there are a number of undesirable consequences of the use of furosemide, of which the pathophysiological mechanisms have not been sufficiently investigated. Furosemide has been associated with worsening of kidney function in patients treated for volume overload admitted for acute heart failure (104) and even glomerular filtration rate (GFR) ...

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Section: Pharmacology Pharmacodynamics Pharmacokinetics Of Furosemidementioning

confidence: 99%

Everything we always wanted to know about furosemide but were afraid to ask

Huang

Mees

Vos

et al. 2016

American Journal of Physiology-Renal Physiology

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“…Solutions of CR candidates were similarly studied in dogs instrumented with a modified Bvascular access port^ (6,9) and by oral administration of a remotely triggered device that would release its payload when in the region of interest (10). The first two methods, although direct and useful, require surgery and regular maintenance.…”

Section: Introductionmentioning

confidence: 99%

Dog Colonoscopy Model for Predicting Human Colon Absorption

et al. 2006

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“…Prominent examples of such devices are Intelisite [3] and Enterion [4]. These capsules contained drug reservoir with capacity of 1 ml that can be emptied remotely.…”

Section: Introductionmentioning

confidence: 99%

Development of a therapeutic capsule endoscope for treatment in the gastrointestinal Tract: Bench testing to translational trial

Stewart¹,

Newton²,

Cox³

et al. 2017

2017 IEEE International Ultrasonics Symposium (IUS)

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-Video capsule endoscopy is a widely accepted clinical alternative to conventional endoscopy for examination of the gastrointestinal tract. Its advantages are that it can visualize the entire gastrointestinal tract including the anatomically remote small intestine and it is less invasive for the patient as compared to conventional endoscopy. However, video capsule endoscopy is suitable only for diagnosis, with little research into therapeutic capsule endoscopy. Like video capsule endoscopy, therapeutic capsule endoscopy has great potential to reach locations that would previously have been difficult, such as the small intestine. Ultrasound-mediated targeted drug delivery is a promising therapeutic capsule based modality as it may be scaled to size, provides temporary gut barrier disruption and power requirement is relatively low. This paper investigates the feasibility of a therapeutic capsule endoscope utilizing ultrasound-mediated targeted drug delivery. A prototype device, SonoCAIT, was built and tested. Further investigation of the drug delivery capabilities of the miniature focused US sources, testing was carried out on an in vitro model replicating the lining of the small intestine. This involved measuring the transepithelial resistance, a measure for barrier function, during insonation. A drop in transepithelial resistance occurred during insonation and returned to starting value post insonation. In anticipation of in vivo work, SonoCAIT, was reconfigured to operate within the small bowel of pigs.

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Evaluation of the Intelisite capsule to deliver theophylline and frusemide tablets to the small intestine and colon

Cited by 47 publications

References 20 publications

Everything we always wanted to know about furosemide but were afraid to ask

Everything we always wanted to know about furosemide but were afraid to ask

Dog Colonoscopy Model for Predicting Human Colon Absorption

Development of a therapeutic capsule endoscope for treatment in the gastrointestinal Tract: Bench testing to translational trial

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