Small bowel Subject

Absence of oats toxicity in small bowel and suggest that the rash observed in DH subjects is not activated by eating oats... 

To investigate the pharmacokinetics (PK) of an XYZ1234 formulation (200 mg) following topical release in the proximal small bowel, distal small bowel and colon via the Enterion capsule in healthy subjects and to compare to the PKof an XYZ1234 immediate release reference formulation (200 mg). 

PK data PK parameters were calculated for all subjects for Regimens A (immediate release), B (proximal small bowel activation) and C (distal small bowel activation). 

The pharmacokinetics of XYZ1234 formulations after release in different regions of the gastrointestinal tract reveal similar exposure for the proximal small bowel as compared to the immediate release formulation, halved exposure for the distal small bowel and only poor absorption from the ascending colon. Thus colonic resorption cannot be relied on for the development of an extended release formulation. Analysis of the scintigraphic data has confirmed release of the formulation at the target locations in the required number of subjects. 

These authors previously found (S12) that in all of 16 women who initially had subnormal serum folate concentrations, serum folate concentrations rose within 3 months after OCAs were stopped. Subsequently they reported (SIO) 3 women with low serum folate levels while taking OCAs and low folate polyglutamate absorption that persisted after medication was discontinued. It was of interest that one of these subjects developed gluten-sensitive enteropathy a year later and a second had a family history of that disease. Other case reports of folate deficiency and mild intestinal malabsorption in users of OCAs have appeared (J3, T2, W12). It should be emphasized, therefore, that evidence of impaired folate absorption in women taking these agents may suggest the presence of inapparent small bowel disease. 

In a case-control study of 11 adults with histologically proven CD and 20 healthy subjects (Table 9.2), Rettenbacher et al. (1999) found that the controls were negative, whereas the cases showed an increase in intraluminal fluid content, the presence of moderate small bowel dilatation, increased peristalsis and moderate bowel wall thickness. Further extra-intestinal signs, such as mesenteric lymph node enlargement, free abdominal fluid, a dilated superior mesenteric artery or portal vein, and hepatic steatosis, were also identified with overall frequencies of 52-84% (Rettenbacher et al. 1999). 

Average single day s diet may contain 10 mg or more copper. Studies indicate that about half of dietary copper is not absorbed but rather excreted in the feces. Absorption and excretion are normally in the range of 1-5 mg daily. The mechanisms by which copper is absorbed and transported by the intestine are unknown. Copper absorption is impaired in severe diffuse diseases of the small bowel, including spruce, lymph sarcoma, and scleroderma. Radioactive copper given by mouth to human subjects appears very rapidly in the blood. 

Comparison between celecoxib and meloxicam with respect to smaU-bowel injury was done in a prospective, double-blind, randomized clinical trial among 29 healthy subjects. They were randomized to receive celecoxib (200 mg twice daily) or meloxicam (10 mg once daily) for two weeks. The incidence and number of small-bowel mucosal injuries (bleedings, ulcers and erosions) as detected by capsule endoscopy were compared between both NSAID groups. The incidence of small-bowel... 

Goldstein JL, Eisen GM, Lewis B, Gratnek IM, Aisenberg J, Bhadra P, et al. Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy. Aliment Pharmacol Ther May 15, 2007 25(10) 1211-22. 

A 49-year-old woman presented with acute abdominal pain and nausea. Abdominal CT scan revealed oedematous small bowel and ascites. She was thought to have intestinal ischaemia and was tiien subjected to a laparotomy which revealed that the intestine was vital with no perforation. ACEl-induced angioedema was suspected when a history of ingestion of lisinopril, 3 days prior to presentation was obtained. Lisinopril was replaced with amlodipine and the pain disappeared after 3 days. 

In healthy subjects the differences in the rate of zinc turnover are relatively small and a standard correction can be made. Otherwise repeated measurements of the rate of excretion can be used to extrapolate retention to absorption values at the time for intake of the meal. The retention measurements is done after two weeks to allow for long bowel transit time. The endogenous extretion of 65 Zn during this period is only about 10%. The radionuctide technique with 65 Zn and whole body counting are described in more detail in an other paper (15). 

Khosla, R. Davis, S.S. Gastric emptying and small and large bowel transit of non-disintegrating tablets in fasted subjects. Int. J. Pharm. 1989, 52, 1-10. 

The fecal clearance of alpha-1-antitrypsin (AT) can also be used as a marker of GI protein loss. AT is a glycoprotein (MW 54,000) that is synthesized in the fiver and is normally present in the serum at a concentration of about 1.5 to 2 g/L. It is a protease inhibitor and therefore resistant to degradation by proteolytic enzymes in the GI tract. The fecal clearance of AT correlates with protein loss measured by Cr techniques (r = 0.96). The correlation is not influenced by serum AT concentrations or by fecal weight. AT clearance can be used for both small and large bowel disease and is appficable to the evaluation of enteric protein loss in children or adults.More recent work has confirmed these findings and also confirmed that fecal AT concentration alone does not reliably predict AT clearance (i.e., a timed fecal sample and measurement of serum AT is required). An important observation is that experimentally induced diarrhea in normal subjects leads to an increased AT clear-... 

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