The effect of liquid fibre on gastric emptying in the rat and humans and the distribution of small intestinal contents in the rat.

Abstract

A combination of the polysaccharide ethylhydroxyethylcellulose (EHEC) and the surfactant sodiumdodecylsulphate (SDS) has the extraordinary physical property of being liquid at room temperature but gelling firmly at 37°C. It has been named 'liquid fibre' and its effect on gastric emptying has been tested in rats and humans, as well as its effect on intestinal distribution in rats. Rats were gavaged with 5 ml of radiolabelled liquid fibre, SDS in water, or water control. Subgroups were killed after 25, 50, 100, 200, and 300 minutes, the gut removed, and the distribution of radioactivity measured scintigraphically. Liquid fibre gelled in the stomach and spread exponentially down the small intestine before 25 minutes. This distribution was maintained for 200 minutes after which the stomach began to empty again. In the human study, 10 healthy men drank 250 ml liquid fibre and placebo labelled with 1.85 MBq technetium tin colioid on separate occasions. Gastric emptying was measured by gammacamera. Haff emptying time significantly increased from 17*7 to 55 8 minutes (means, p<005). The time for 10% to empty (which includes any lag time) increased from 7 0 to 19*4 minutes (p<005). Average emptying rate decreased from 4-49%/min for placebo to 1-60%/min for liquid fibre (p<0 01). The dramatic delay in gastric emptying suggests liquid fibre may have clinical applications while its liquid formulation should improve acceptability.

The effect of the gel-forming liquid fibre on feeding behaviour in man

“…It has been shown using y-scintigraphy that LF stays in the human stomach for much longer than does a placebo drink (half-emptying times, 55.8 and 17.7 min respectively). It also converts the gastric emptying profile from an exponential curve typical of a liquid into a linear form with a lag period which is typical of a solid emptying profile (Tomlin et al 1993). It is postulated that if LF is taken before a meal it should distend the stomach and thus cause a physical signal to reduce hunger, induce early satiation and so reduce food intake.…”

Utilizing a Novel Tandem Oral Dosing Strategy to Enhance Exposure of Low-Solubility Drug Candidates in a Preclinical Setting

“…Based on this assumption, we hypothesized that if each dose is less than 300 mg/ kg and administered in a tandem dose scheme, the high FA (for each dose) and short dose frequency (every 2.5 h) would allow drug exposure to build up very quickly (both AUC and C max ). The 2 1 = 2 h dose interval was chosen based on the literature reviews [12][13][14][15][16][17][18][19][20][21][22] and in-house data (not included). This dose interval should be sufficient to separate two doses (represented by the geometric mean of the unabsorbed drug at the moment) from each compartment (i.e., stomach and duodenum).…”

“…Several researches have reported the GI transit time of small lab animals. [12][13][14][15][16][17][18][19][20][21][22] Based on those reported values and in-house data, the GI transit time for a rat is anywhere from 2.5 to 12 h. The dose interval of 2-3 h should be sufficient to separate two doses from each compartment. Thus, an absorbable amount of drug can be dosed every 2-3 h (as a ''tandem'' dose) without having significant dose overlap.…”

Investigação da atividade antihiperglicemiante da farinha da casca de Passiflora edulis Sims, Passifloraceae, em ratos diabéticos induzidos por aloxano

“…Este período de tempo entre o efeito e a administração das fibras solúveis, observado no presente estudo e descrito por Kamgang et al (2008), pode indicar que o tempo de esvaziamento gástrico interfere no inicio do efeito antihiperglicemiante de substâncias que tenham seu mecanismo de ação mediado pela formação de gel ao nível do intestino, uma vez que observa-se um aumento significativo deste parâmetro após o consumo de fibras solúveis, passando de 20 para 200 minutos (Tomlin et al, 1993).…”