Gastrointestinal tract variation

Considering the importance of the gastrointestinal tract for the entry of essential compounds into the body, it is surprising that its function is so rarely impaired by the massive variations in quantity and composition of the food consumed by humans. Nonetheless, when it is impaired the consequences can be severe. Examples are ... 

This variation may be a result of (1) a real difference in children s intake of soil, (2) that the intake of the various tracer elements are not only from soil, but also from food or other objects which children put into their mouth, (3) errors in sampling excreta, primarily feces, from the diaper, (4) tracer elements that are transferred to feces via contact with the diaper, e.g., from certain skin lotions, (5) a difference in absorption of the various tracer elements from the gastrointestinal tract, and (6) the collected soil samples that are usually inhomogeneous and not representative of an average exposure. 

Propranolol is well absorbed from the gastrointestinal tract, but it is avidly extracted by the liver as the drug passes to the systemic circulation (first-pass effect). This effect explains the large variation in plasma levels of propranolol seen after oral drug administration. 

Since hepatobiliary and intestinal dysfunctions are marked by variation in the concentration and relative proportions of major BAs and by increased levels of their minor forms, individual identification and accurate quantification of these compounds in biological samples are very important prognostic, diagnostic, and therapeutic monitoring indicators of liver and gastrointestinal tract diseases in humans. 

Piperazine and its salts are readily absorbed from the gastrointestinal tract, but nitrosation may occur in the stomach (32). The major portion of the absorbed drug is metabolized in tissues and the remainder, which is about 30-40%, is excreted in the urine. Piperazine is detectable in the urine as early as 0.5 h after drug administration. Although there is a wide variation in the rates at which piperazine is excreted by different animal species, urinary excretion is practically complete within 24 h. 

Assimilation from the Gastrointestinal Tract. There are several sources of variation in the assimilation of actinides from the mammalian intestine. Among the most important are chemical form and age of the animal. The comparative metabolism of different actinides administered to rats as nitrates has been studied by Sullivan and Crosby (25,26). The consistency of experimental technique in their administration of actinides to adult and newborn rats permits comparisons between the assimilation of different actinides. The fractional assimilation, expressed as the amount in liver and carcass together, 7 days post-dose, was approximately IO for isotopes of U, Pu, Am and Cm in adult rats. In young rats, the assimilation was about two orders of magnitude greater. 

The pH of the gastrointestinal tract varies, being 1-2 in the stomach, 5-6 in the duodenum, 6-7 in the jejunum, 7-8 in the ileum, and 8-9 in the large intestine. This variation in pH influences the extent to which acidic or basic chemical substances are ionized, which influences the extent of their absorption. The degree of ionization of an acidic substance or a basic substance at a given pH can be expressed by the Henderson-Hasselbalch equations (equations (2) and (3), respectively) ... 

Most NSAIDs are well absorbed from the gastrointestinal tract, although there can be substantial inter- and intra-individual variations, e.g. indometacin [1, 24],... 

Absorption of theophylline from the gastrointestinal tract is usually rapid and complete. Some 90% is metabolised by the liver and there is evidence that the process is saturable at therapeutic doses. The tis 8 h, with substantial variation, and it is prolonged in patients with severe cardiopulmonary disease and cirrhosis. Obesity and prematurity are associated with reduced rates of elimination, whereas tobacco smoking enhances theophylline clearance by inducing hepatic P450 enzymes. Because of these pharmacokinetic factors and low therapeutic index, monitoring of the plasma theophylline concentration is necessary to optimise its therapeutic effect and minimise the risk of adverse reactions the optimum concentration range is 10-20 mg/1 (55-110 mmol/1). 

Mixture models (such as those of Scheffe) are still useful, especially when there are three or more such excipients with fairly large ranges of variation. In solid formulations, this is often the case for diluents (or fillers) and also for the polymers or waxes incorporated into controlled-release tablets to form a matrix through which the drug diffuses slowly out when immersed in aqueous fluid, i.e., in the gastrointestinal tract. 

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. 

---