Intestinal transit times

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... 

LX Yu, GL Amidon. Characterization of small intestinal transit time distribution in humans. Int J Pharm 171 157-163, 1998. 

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. 

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]. 

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

Fallingborg, J., Pedersen, F., Jacobsen, B. A., Small intestinal transit time and intraluminal pH in ileocecal resected patients with Crohn s disease, Dig. Dis. Sci. 1998, 43, 702-705. 

In the small intestine, contact time with the absorptive epithelium is limited, and a small intestinal transit time (SITT) of 3.5-4.5 hr is typical in healthy volunteers. The Holy Grail of drug delivery would be to discover a mechanism that... 

Caride VJ, Prokop EK, Troncale FJ, Buddoura W, Winchen-bach K, McCallum RW. Scintigraphic determination of small intestinal transit time comparison with the hydrogen breath technique. Gastroenterology 1984 86 714-720. 

The basis for all CAT models is the fundamental understanding of the transit flow of drugs in the gastrointestinal tract. Yu et al. [61] compiled published human intestinal transit flow data from more than 400 subjects, and their work showed the human mean small intestinal transit time to be 199 min. and that seven compartments were optimal in describing the small intestinal transit process using a compartmental approach. In a later work, Yu et al. [58] showed that between 1 and 14 compartments were needed to optimally describe the individual small intestine transit times in six subjects but in agreement with the earlier study, the mean number of compartments was found to be seven. This compartmental transit model was further developed into a compartmental absorption and transit (CAT) model ([60], [63]). The assumptions made for this CAT model was that no absorption occurs in the stomach or in the colon and that dissolution is instantaneous. Yu et al. [59] extended the CAT model... 

J. H. Cummings, Ft. S. Wiggins, D. J. A. Jenkins, H. Houston, T. Jivraj, B. S. Drasar and M. J. Hill, Influence of diets high and low in animal fat on bowel habit, gastro-intestinal transit time, fecal microflora, bile acid, and fat excretion, J. Clin. Invest., 1978, 61, 953. 

Uicerative coiitis Agents that inhibit intestinal motility or delay intestinal transit time have induced toxic megacolon. Consequently, carefully observe patients with acute ulcerative colitis. 

---