Transit, intestinal

Phyto chemicals can be used to either stimulate or inhibit motility of the GIT. For example, caffeine and other phytochemicals stimulate motility (Lis-Balchim etal, 2001 Boekema et al, 1999), whereas motility is slowed by peppermint oil (Beesley et al, 1996), protease inhibitors (Schwartz et al., 1994) and several other phytochemicals (Abdullahi et al, 2001 Odetola and Acojenu, 2000 Rojas et al, 1999 Amos et al, 1998). Many of the traditional herbal medicines used for treatment of diarrhea are based on aqueous extracts that slow small intestine transit and increase residence time for digesta (Lin et al, 2002). The opiates and derivatives are particularly noteworthy (Williams et al., 1997). 

SITT small intestinal transit time (4.5h = 270min)... 

Crison and Amidon [47,48] recently used the mass balance approach to study the variability in absorption due to intestinal transit time for water-insoluble drugs. As expected, for low dose drugs, such as digoxin, the variability in absorption sharply decreases with the increase of dissolution number via micronization. For high dose drugs, such as griseofulvin, little effect was observed when the dissolution number was increased by micronization. 

In order to determine the optimal number of compartments, literature information on small intestinal transit times was utilized. A total of over 400 human small intestinal transit time data were collected and compiled from various publications, since the small intestinal transit time is independent of dosage form, gender, age, body weight, and the presence of food [70]. Descriptive statistics showed that the mean small intestinal transit time was 199 min with a standard deviation of 78 min and a 95% confidence interval of 7 min. The data set was then analyzed by arranging the data into 14 classes, each with a width of 40 min. Figure 9 shows the distribution of this data set. 

Figure 9 Distribution of small intestinal transit time in humans. The transit time was measured by y-scintigraphy based on the difference in time between 50% of the drug arriving at the colon and 50% of the drug leaving the stomach. The distribution was constructed from over 400 literature data points. (From Ref. 64 with kind permission from Elsevier Science-NL, Amsterdam.)...

F(t) Cumulative distribution of the small intestinal transit time... 

RL Oberle, GL Amidon. The influence of variable gastric emptying and intestinal transit rates on the plasma level curve of cimetidine An explanation for the double peak phenomenon. J Pharmacok Biopharm 15 529-544, 1987. 

LX Yu, JR Crison, GL Amidon. Compartmental transit and dispersion model analysis of small intestinal transit flow in humans. Int J Pharm 140 111-118, 1996. 

Although it appears that severe IL-4-regulated enteropathy is not required for immune expulsion of T. spiralis, it is still possible that Th2 cytokines can act in a direct fashion to create an environment unfavourable for intestinal parasites. It remains to be shown directly whether these effects are sufficient to expel parasites. Indeed, there is considerable evidence to support a variety of pathophysiological effects of IL-4 and/or TNF on the gut. These effects may be mediated by factors including cytokines and mast-cell products (e.g. leukotrienes and 5-hydroxytryptamine). 7. spiralis infections result in increased fluid and mucus secretion into the lumen as well as increased intestinal propulsive activity and more rapid intestinal transit (Castro et al, 1979 Russell, 1986 Vermillion and Collins, 1988 Vermillion et al., 1991 Weisbrodt et al, 1994 Barbara et al, 1997). The increased contractility of radial and longitudinal muscle is greater in high-... 

SIWV = small intestinal water volume (mL), assumed to be c. 250 mL SITT = small intestinal transit time (min), assumed to be 4.5 h = 270 min. 

Fig. 8.4. Fasting small-intestinal pH data over a 3 h period of intestinal transit. Graph constructed from data in Youngberg et al. [63],...

The ACAT model is loosely based on the work of Amidon and Yu who found that seven equal transit time compartments are required to represent the observed cumulative frequency distribution for small intestine transit times [4], Their original compartmental absorption and transit (CAT) model was able to explain the oral plasma concentration profiles of atenolol [21]. 

Kaiampokis, A., Argyrakis, P., Macheras, P., Heterogeneous tube model for the study of small intestinal transit flow, Pharm. Res. 1999, 16, 87-91. 

A special case in dissolution-limited bioavailability occurs when the assumption of sink condition in vivo fails that is, the drug concentration in the intestine is dose to the saturation solubility. Class IV compounds, according to BCS, are most prone to this situation due to the combination of low solubility and low permeability, although the same could also happen for class II compounds, depending primarily on the ratio between dose and solubility. Non-sink conditions in vivo lead to less than proportional increases of bioavailability for increased doses. This is illustrated in Fig. 21.8, where the fraction of drug absorbed has been simulated by use of an compartmental absorption and intestinal transit model [35] for different doses and for different permeabilities of a low-solubility, aprotic compound. 

S. K., Effect of dosing time on the total intestinal transit time of nondisintegrating systems, Int. J. Pharm. 2000, 204, 47-51. 

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