Gastrointestinal system study

These studies represent the first report of the metabolism of brevetoxins by mammalian systems. PbTx-3 was rapidly cleared from the bloodstream and distributed to the liver, muscle, and gastrointestinal tract. Studies with isolated perfused livers and isolated hepatocytes conflrmed the liver as a site of metabolism and biliary excretion as an important route of toxin elimination. [ H]PbTx-3 was metabolized to several compounds exhibiting increased polarity, one of which appeared to be an epoxide derivative. Whether this compound corresponds to PbTx-6 (the 27,28 epoxide of PbTx-2), to the corresponding epoxide of PbTx-3, or to another structure is unknown. The structures of these metabolites are currently under investigation. 

Sato et al. (1991) expanded their earlier PBPK model to account for differences in body weight, body fat content, and sex and applied it to predicting the effect of these factors on trichloroethylene metabolism and excretion. Their model consisted of seven compartments (lung, vessel rich tissue, vessel poor tissue, muscle, fat tissue, gastrointestinal system, and hepatic system) and made various assumptions about the metabolic pathways considered. First-order Michaelis-Menten kinetics were assumed for simplicity, and the first metabolic product was assumed to be chloral hydrate, which was then converted to TCA and trichloroethanol. Further assumptions were that metabolism was limited to the hepatic compartment and that tissue and organ volumes were related to body weight. The metabolic parameters, (the scaling constant for the maximum rate of metabolism) and (the Michaelis constant), were those determined for trichloroethylene in a study by Koizumi (1989) and are presented in Table 2-3. 

Zweibaum A, M Laburthe, E Grasset, D Louvard. (1991). Use of cultured cell lines in studies of intestinal cell differentiation and function. In M Field, CA Frizzell, eds. Handbook of Physiology, Section 6, The Gastrointestinal System, Vol. IV, Intestinal Absorption and Secretion. Bethesda, MD Am Physiol Society, pp 223-255. 

In a study reported by the National Cancer Institute (NCI 1980), rats exposed to 16-1,694 mg/kg/day and mice exposed to 25-2,642 mg/kg/day phenol in drinking water exhibited no indication of histopathological effects on the gastrointestinal system after 13 weeks of exposure. No histological abnormalities of the gastrointestinal tract were observed in rats or mice exposed to 2,500 or 5,000 mg/L phenol in drinking water for 103 weeks (mg/kg/day doses 322 or 645 for male rats 360 or 721 for female rats 590 or 1,180 for male mice 602 or 1,204 for female mice) (NCI 1980). 

The most prominent pharmacologic effects of cholinesterase inhibitors are on the cardiovascular and gastrointestinal systems, the eye, and the skeletal muscle neuromuscular junction (as described in the Case Study). Because the primary action is to amplify the actions of endogenous acetylcholine, the effects are similar (but not always identical) to the effects of the direct-acting cholinomimetic agonists. 

Takemura, S., Watanabe, S., Katsuma, M., and Fukul, M. (2002), Gastrointestinal transit study of a novel colon delivery system (CODES ) using gamma scintigraphy, Proc. Int. Symp. Controlled Release Bioactive Mater., 27, 445-446. 

Blanquet, S., Zeijdner, E., Beyssac, E., Meunier, J. P., Denis, S., Havenaar, R., and Alric, M. (2004), A dynamic gastrointestinal system for studying the behavior of orally administered drug dosage forms under various physiological conditions, Pharm. Res., 21, 585-591. 

Cancer at Other Sites. Mortality studies of asbestos workers have revealed small increases in the incidence of death from cancer at one or more sites other than the lung, the pleura, or the peritoneirm, mostly in tissues of the gastrointestinal system. For example, a total of 99 deaths from cancers of the esophagus, stomach, colon, or rectum were observed in a cohort of 17,800 insulation workers, while only... 

Results of various in vitro and in vivo bioaccessibility studies (Ruby et al, 1993, 1996, 1999 Davis et al, 1992, 1996, 1993 Borch et al, 1994 Dieter etal, 1993) indicate that some aspects of the fate of metals or metalloids leached from mine wastes that enter the gastrointestinal system can be readily understood based on their mineralogical characteristics, coupled with a knowledge of how... 

In a review of 12 clinical studies most of the adverse events in those taking azithromycin affected the gastrointestinal system, and were reported in 138 (8.5%) azithromycin-treated patients (29). Abdominal pain, diarrhea, nausea, and vomiting were the most frequently reported gastrointestinal adverse events. 

The safety and efficacy of oxcarbazepine 600-2400 mg/ day as adjunctive therapy for uncontrolled partial seizures have been studied in a randomized, double-bhnd, placebo-controUed study in 694 patients aged 15-65 years (7). During the double-bhnd phase, 76%, 84%, 90%, and 98% of patients respectively taking placebo or oxcarbazepine 600,1200, or 2400 mg/day reported one or more adverse events. The most common adverse events were related to the nervous and gastrointestinal systems. 

Gastrointestinal Effects. Oral exposure to hydrazine has produced nausea and vomiting in human cancer patients. These effects could be due to direct irritation of the gastrointestinal tract but could also be due to effects on the central nervous system. Studies in animals generally have not reported effects on the gastrointestinal system following intermediate and chronic inhalation exposures to 25 ppm... 

---