Gastrointestinal tract transit time

The fecal elimination is caused by the enterohepatic biliary recirculation of indapamide metabolites which in some subjects can be continued for 96 hours (25). However, elimination is essentially complete after 144 hours. The slow elimination in man may be due to enterohepatic recirculation and the long gastrointestinal tract transit time (24). Metabolic products in the feces are at least, a molecular weight of 500 indicating probable glucuronide and sulphate conjugates (26). 

Real-time monitoring during consumption of foods, to ascertain the site and the rate of release of bioactives using nondestructive methods will be needed to help develop models to link structure to breakdown during gastrointestinal tract transit. The substantiation of health claims is central to the provision of evidence-based interventions based on food. Human-based trials will be needed to provide unequivocal evidence of bioactive performance. 

Other than the different approaches mentioned above, commercial packages such as GastroPlus (Simulations Plus, Lancaster, CA) [19] and IDEA (LionBioscience, Inc. Cambridge, MA) [19] are available to predict oral absorption and other pharmacokinetic properties. They are both based on the advanced compartmental absorption and transit (CAT) model [20], which incorporates the effects of drug moving through the gastrointestinal tract and its absorption into each compartment at the same time (see also Chapter 22). 

The important stages in delivering a drug to its desired target after an oral dose can be summarized as shown in Fig. 6.2. Initially the formulation has to be swallowed and survive the transition to the site of absorption - the gastrointestinal tract (GIT). The time required for this to happen will depend on the stomach emptying time, which in turn will be a function of the fed/fasted state of the subject or animal that is being studied (see for example Ref. [7]). This kind of information can only be obtained from in vivo studies. 

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... 

HT3 receptors in the gastrointestinal tract activate visceral afferent pain sensation via extrinsic sensory neurons from the gut to the spinal cord and central nervous system. Inhibition of afferent gastrointestinal 5-HT3 receptors may inhibit unpleasant visceral afferent sensation, including nausea, bloating, and pain. Blockade of central 5-HT3 receptors also reduces the central response to visceral afferent stimulation. In addition, 5-HT3-receptor blockade on the terminals of enteric cholinergic neurons inhibits colonic motility, especially in the left colon, increasing total colonic transit time. 

The extent of absorption of an administered dose has been found to be associated with transit time through the gastrointestinal tract the authors report that this may explain some of the interspecies differences in silver retention observed 1 week after exposure (see Table 2-3). The faster the transit time, the less silver is absorbed (Furchner et al. 1968). Transit times vary from about 8 hours in the mouse and rat to approximately 24 hours in the monkey, dog, and human (Furchner et al. 1968). 

SPIOs are used for gastrointestinal tract, liver, and spleen imaging and take advantage of the natural clearance of the RES, the transit time through the gut or preferential uptake by specific cells. The most promising uses of SPIOs are to improve the sensitivity of detection and localization of primary and metastatic brain tumors, inflammation and ischemia (insufficient supply of blood to an organ) [154-156],... 

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. 

He, P. Davis, S.S. Ihum, L. Chitosan microspheres prepared by spray drying. Int. J. Pharm. 1999,187, 53-65. Rechgaard, H. Beggsen, S. Distribution of pellets in the gastrointestinal tract. The influence of transit time exerted by density or diameter of pallets. J. Pharm. Pharmacol. 1978, 30, 690. 

In most cases, oral drug delivery is the cheapest and most convenient method of dosing. Unfortunately, it is difficult to achieve a precise control of the plasma-concentration-time profile by this route due to marked intra- and intersubject variation in gastrointestinal transit even under the rigidly controlled conditions of the clinical trial. Daily patterns of food intake, activity, and posture are large contributors to this variation. Drugs that are only absorbed from specific areas of the gastrointestinal tract, i.e., have a narrow window of absorption, will be most affected by alterations in transit. The major determinants of this variation will be the amount of food and drink consumed. 

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