Small intestine transit time

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

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]. 

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... 

I.c.v. and i.t. administration of the 5 opioid agonist deltorphin II in rodents inhibits diarrhea and colonic bead expulsion in a dose-dependent manner but does not delay small intestine transit time. 5 agonists have been found to mediate mainly antisecretory effects and influence gut motility only marginally. These effects can be antagonized by pretreatment with NTI (Shook et al. 1989). 

Poly(vinyl alcohol)-gel spheres with chitosan (PVA-GS/Ch) or without chitosan (PVA-GS) were prepared to control the GI transit time of drugs, and their particles were 5-10 pm [26]. PVA-GS/Ch displayed a longer small-intestinal transit time than PVA-GS. The transit rate was considered to decrease by the adhesion of chitosan to the intestinal mucus layer. PVA-GS/Ch and PVA-GS were loaded with theophylline and ampicillin. These released the drugs in a similar manner. The drugs were released almost completely at 4 h after the start of the release test. Both the gel spheres containing theophylline exhibited a bioavailability similar to that of the theophylline solution. Also, the bioavailability of ampicillin was greater in PVA-GS/Ch than in the PVA-GS and ampicillin solution the bioavailability of PVA-GS/Ch was approximately 150% of that of ampicillin solution (Table 3.2). As theophylline is rapidly absorbed in... 

The first fraction of the previous equation shows that An is exclusively determined by the effective permeability Peff of drug since all other variables are species-dependent physiological parameters. In terms of characteristic times, the An of a drug can also be defined as the ratio of the mean small intestinal transit time (Tsi), to its absorption time R/Peff. 

Analysis of experimental human small-intestine transit time data collected from 400 studies revealed a mean small-intestinal transit time (TSi) = 199 min [173]. Since the transit rate constant kt is inversely proportional to (TSj), namely, kt = to/ (TSi), (6.12) was further fitted to the cumulative curve derived from the distribution frequency of the entire set of small-intestinal transit time data in order to estimate the optimal number of mixing tanks. The fitting results were in favor of seven compartments in series and this specific model, (6.10) and (6.11) with to = 7, was termed the compartmental transit model. 

This equation allows one to consider the cumulative distribution of small-intestinal transit time data with respect to the fraction of dose entering the colon as a function of time. In this context, this equation characterizes well the small-intestinal transit data [173, 174], while the optimum value for the dispersion coefficient D was found to be equal to 0.78 cm2 s 1. This value is much greater than the classical order of magnitude 10 5 cm2 s 1 for molecular diffusion coefficients since it originates from Taylor dispersion due to the difference of the axial velocity at the center of the tube compared with the tube walls, as depicted in Figure 6.5. 

Small intestinal transit times for the Enterion capsule were on average 4.19 h for Regimen B, 4.69 h for Regimen C and 4.11 h for Regimen D. 

Mean small intestinal transit times for the Enterion capsule of 4.19 1.19, 4.69 1.71 and 4.11 1.45 h for Regimens B, C and D, respectively, are not unusual. There is always a high degree of intra- and inter-subject variability observed in gastrointestinal tract data. These intestinal transit times are in general agreement with the 3 h ( 1 h, range 1.3 to 6 h) previously reported for solutions, pellets and tablets. 

Time-controlled systems. These systems rely on the relatively consistent small intestinal transit time, which approximates between 3 and 5h. Obviously, drug release from such systems occurs after a predetermined lag phase (i.e., >5h), which can be precisely programmed by adjusting the thickness and/or composition of the barrier (e.g., coating) formulation. Examples... 

Excipients such as mannitol can affect small intestinal transit, which in turn can affect the absorption of certain drugs. Oral solutions are rarely likely to fall short of bioequivalence relative to solid oral formulations, although during the development of a ranitidine effervescent oral solution dosage form containing sodium acid pyrophosphate (SAPP), a marked decrease in absorption was observed in the extent of ranitidine absorption from the liquid formulation relative to the conventional oral tablet. The formulation contained 150 mg ranitidine with 1132 mg SAPP together with 1.5 MBq hndium chloride solutions. Small intestinal transit time was decreased to 56% in the presence of the excipient. The rapid small intestinal transit associated with an excipient of a solution dosage form resulted in a decreased extent of ranitidine absorption. " ... 

Very few data are available on gastrointestinal pH in children. In 12 healthy subjects aged 8-14 years, the mean gastric pH was 1.5 and duodenal pH was 6.4, but this gradually rose in the small intestine reaching a peak value of 7.4 in the distal ileum.The pH dropped to 5.9 as the pH radiotelemetry capsule entered the caecum but increased to 6.5 in the rectum. The median gastric residence time of the telemetry capsule was 1.1 h, small intestinal transit time was 7.5 h, and colonic transit time was 17.2 h. 

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