Gastrointestinal variables

Orally administered dosage forms are absorbed into the systemic circulation following dissolution in the GI tract. Because substances must be in solution for the absorption from the GI lumen, the absorption rate of poorly water-soluble drugs is limited by their rate of dissolution. The dissolution rate is affected by the unique physicochemical properties of the drug and by physiological factors the pH, composition, and hydrodynamics of the GI medium. 

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BMI 19.8-36.0 kg m-2) were studied. All transit variables were unaffected by gender. The older subjects had a slower mean colonic transit time of radiolabeled plastic particles than the young subjects (p < 0.05), while BMI affected the gastric emptying of fiber but not other gastrointestinal variables [22]. In a more recent study, comparison was made between cohorts of young and elderly males, but no age-related effect could be determined [23]. 

M. G. Choc and W. T. Robinson, Gastrointestinal variables and water insoluble compounds in normal and disease states, Presentation to the AAPS/CRS/FDA workshop on scientific foundation and applications for the biopharmaceutics classification and in vitro-in vivo correlations, April 14-16, 1997, Arlington VA. 

Normal Rabbits. Six male, white rabbits (2.5 - 3.0 kg) were housed individually. Animals were fasted overnight for 16 hours (with access to water) prior to each experiment to reduce the gastrointestinal content and absorption variability. After treatment with either a control dose or experimental insulin in poly(acrylic acid) resin dose, a one week washout period was required before the next experiment. The protocol called for blood samples to be taken from an indwelling ear catheter at -1, -.5, -.25, +.5, +1, +1.5, +2, +3, +4, +5 and +6 hours. Serum glucose levels were determined by an oxidase colorimetric method using the Sigma 510 Glucose Kit. 

Parenteral administration of drugs by intravenous (IV), intramuscular (IM), or subcutaneous (SC) routes is now an established and essential part of medical practice. Advantages for parenterally administered drugs include the following rapid onset, predictable effect, predictable and nearly complete bioavailability, and avoidance of the gastrointestinal (GI) tract and, hence, the problems of variable absorption, drug inactivation, and GI distress. In addition, the parenteral route provides reliable drug administration in very ill or comatose patients. 

Interroute extrapolation. The values for pharmacokinetic variables in the O Flaherty Model are independent of the route of exposure. However, the model does incorporate media-specific estimates of absorption from the gastrointestinal tract. Different exposure scenarios have been evaluated with the O Flaherty Model for children and adults (O Flaherty 1993, 1995a). 

Di Lorenzo C, Dooley CP, Valenzula JE Role of fasting gastrointestinal motility in the variability of gastrointestinal transit time assessed by hydrogen breath test. Gut 1991 32 1127-1130. 

Bismuth compounds have been used for treating gastrointestinal disorders for more than two centuries (451). These include bicarbonate, nitrate and salicylate salts, and colloidal bismuth subcitrate. These are all Bi(III) compounds Bi(V) is usually a strong oxidant. Their structures are largely unknown and often contain a mixture of anionic ligands. This reflects the strong tendency of Bi(III) to hydrolyze and form stable hydroxo and oxo complexes. The first pKa of Bi(III) in water is ca. 1.5. Bismuth(III) has a variable coordination number, from 3 to 10. 

Since ferrets eat only their caloric requirements, and since their gastrointestinal transit time is short (3-5 h), it is recommended that they receive diet ad libitum. Dry cat food was previously recommended for ferrets however, there are now at least two standardized ferret chows commercially available. The most important dietary variable is the quality of the protein, and ferrets appear to do best with a high percentage of animal protein in their diet (Morton and Morton, 1985). Feed consumption will be higher in the fall and winter and lower in the spring and... 

An acute intravenous study can provide accurate rates of metabolism without interference from intestinal flora, plus rates of renal and biliary elimination, if urine and bile are collected. This route also avoids the variability in delivered dose associated with oral absorption and ensures that the maximum amount of radiolabel is excreted in the urine or bile for purposes of detection. Once IV data and parameters are available, they can be used with plasma concentrations from limited oral studies to compute intestinal absorption via the ratio of Areas Under the (plasma and/or urine) Curves or via simulations of absorption with gastrointestinal absorption models. 

ROCK C L, THORNQUIST M D, KRISTAL A R, PATTERSON R E, COOPER D A, NEUHOUSER M L, neumark-sztainer D and cheskin l j (1999), Demographic, dietary and lifestyle factors differentially explain variability in serum carotenoids and fat-soluble vitamins baseline results from the sentinel site of the Olestra Post-Marketing Surveillance Study , J Nutr, 129(4), 855-64. rodale (1996), The Prevention Index - a report card on the nation s health, 1996 summary report. Rodale Press, Inc, Emmaus, Pennsylvania. SANDLER R S, ZORICH N L, FILLOON T G, WISEMAN H B, LIETZ D J, BROCK M H, ROYER M G and MIDAY R K (1999), Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides , Annals Internal Med, 130, 253-61. 

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