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BACKGROUND: Intestinal morphology and function vary geographically. AIMS: These functions were assessed in asymptomatic volunteers in European, North American, Middle Eastern, Asian, African, and Caribbean countries. METHODS: Five hour urine collections were obtained from each subject following ingestion of a 100 ml iso-osmolar test solution containing 3-0-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose after an overnight fast, to assess active (3-0-methyl-D-glucose) and passive (D-xylose) carrier mediated, and non-mediated (L-rhamnose) absorption capacity, as well as intestinal permeability (lactulose:rhamnose ratio). RESULTS: A comparison of results for subjects from tropical countries (n=218) with those resident in the combined temperate and subtropical region (Europe, United States, Qatar) (n=224) showed significant differences. Residents in tropical areas had a higher mean lactulose:rhamnose ratio and lower mean five hour recoveries of 3-0-methyl-D-glucose, D-xylose, and L-rhamnose, indicating higher intestinal permeability and lower absorptive capacity. Investigation of visiting residents suggested that differences in intestinal permeability and absorptive capacity were related to the area of residence. Subjects from Texas and Qatar, although comprised of several ethnic groups and resident in a subtropical area, showed no significant difference from European subjects. CONCLUSIONS: There are clearly demarcated variations in intestinal permeability and absorptive capacity affecting asymptomatic residents of different geographical areas which correspond with the condition described as tropical enteropathy. Results suggest the importance of environmental factors. The parameters investigated may be relevant to the predisposition of the indigenous population and travellers to diarrhoeal illness and malnutrition. Intestinal function in patients from the tropics may be difficult to interpret, but should take into account the range of values found in the asymptomatic normal population.

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UNLABELLED: Intestinal permeability can be assessed non-invasively using the lactulose-rhamnose (L-R) test, which is a reliable measure of small intestinal integrity. AIMS: To determine risk factors for abnormal intestinal permeability in kwashiorkor, and to measure changes in L-R ratios with inpatient rehabilitation. DESIGN: A case-control study of 149 kwashiorkor cases and 45 hospital controls. The L-R test was adapted to study kwashiorkor in Malawi, with testing at weekly intervals during nutritional rehabilitation. Urine sugars were measured by thin layer chromatography in London. RESULTS: The initial geometric mean L-R ratios (x100) (with 95% confidence interval) in kwashiorkor were 17.3 (15.0 to 19.8) compared with 7.0 (5.6 to 8.7) for controls. Normal ratios are < 5, so the high ratios in controls indicate tropical enteropathy syndrome. Abnormal permeability in kwashiorkor was associated with death, oliguria, sepsis, diarrhoea, wasting and young age. Diarrhoea and death were associated with both decreased L-rhamnose absorption (diminished absorptive surface area) and increased lactulose permeation (impaired barrier function) whereas nutritional wasting affected only L-rhamnose absorption. Despite, clinical recovery, mean L-R ratios improved little on treatment, with mean weekly ratios of 16.3 (14.0 to 19.0), 13.3 (11.1 to 15.9) and 14.4 (11.0 to 18.8). CONCLUSION: Abnormal intestinal permeability in kwashiorkor correlates with disease severity, and improves only slowly with nutritional rehabilitation.

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UNLABELLED: The dual sugar test of intestinal permeability is a reliable non-invasive way of assessing the response of the small intestinal mucosa to nutritional rehabilitation. AIM: To compare a local mix of maize-soya-egg to the standard milk diet in the treatment of kwashiorkor. DESIGN: The diets were alternated three monthly in the sequence milk-maize-milk. There were a total of 533 kwashiorkor admissions of at least five days during the study who received either milk or maize. Intestinal permeability was assessed at weekly intervals by the lactulose-rhamnose test in 100 kwashiorkor cases, including 55 on milk and 45 on the maize diet. RESULTS: Permeability ratios (95% confidence interval) on the milk diet improved by a mean of 6.4 (1.7 to 11.1) compared with -6.8 (-16.8 to 5.0) in the maize group. The improved permeability on milk occurred despite more diarrhoea, which constituted 34.8% of hospital days (29.8 to 39.8) compared with 24.3% (17.8 to 30.8) in the maize group. Case fatality rates for all 533 kwashiorkor admissions were 13.6% v 20.9%, respectively, giving a relative risk of death in the maize group of 1.54 (1.04 to 2.28). The maize group also had more clinical sepsis (60% v 31%) and less weight gain (2.9 v 4.4 g/kg/day) than the milk group. IMPLICATIONS: Milk is superior to a local maize based diet in the treatment of kwashiorkor in terms of mortality, weight gain, clinical sepsis, and improvement in intestinal permeability.

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OBJECTIVES: Body weight is regulated by the balance between energy intake and energy expenditure, but the influence of HIV infection on energy balance has not been fully examined. The main objectives of this study were (1) to assess the effect of HIV on energy balance, (2) to examine the relationship of parameters of immunodeficiency to energy balance, and (3) to examine the interrelationship of different components of energy balance in asymptomatic HIV-seropositive men. DESIGN: A cross-sectional study of nutrition and metabolism in asymptomatic HIV-seropositive men METHODS: Components of energy balance were examined in 104 asymptomatic HIV-seropositive men (CD4 count 4-482 x 10(6)/l) and 57 age-matched HIV-seronegative male controls. Energy and protein intake were measured using 5-day diaries, and small bowel absorption and permeability was assessed using four sugar probes. Resting energy expenditure was calculated from indirect calorimetry and nitrogen loss estimated from 24 h urine collection. Four methods were used to assess the effect of HIV infection on body composition (anthropometry, dual energy X-ray absorptiometry, bioelectrical impedance and 24 h urine creatinine). RESULTS: Resting energy expenditure per kilogram of fat-free mass was raised (P < 0.0001), fat mass was decreased (P = 0.001), fat-free mass was increased (P = 0.05), energy intake was higher (P = 0.05), absorption of L-rhamnose (P = 0.01) and 3-O-methyl-D-glucose was decreased (P = 0.003), and small bowel permeability was increased (P < 0.0001) in HIV-seropositive men compared with HIV-seronegative controls. HIV-seropositive subjects with a CD4 count less than 100 x 10(6)/l had decreased absorption of L-rhamnose (P < 0.05), D-xylose (P < 0.05) and 3-O-methyl-D glucose (P < 0.05) compared with HIV-seropositive subjects at higher CD4 counts, and had a similar resting energy expenditure to HIV-seronegative controls. Protein intake, carbohydrate, fat and protein oxidation. 24 h nitrogen excretion and appendicular muscle mass were similar in HIV-seropositive men and controls. CONCLUSION: HIV infection exerts a direct effect on parameters of energy balance that varies with the severity of immunosuppression.

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OBJECTIVES: This study examines small intestinal absorption-permeability, intestinal inflammation and ileal structure and function in HIV-positive male homosexuals. METHODS: Thirty HIV-seropositive male homosexuals at various stages of disease underwent intestinal absorption permeability and 111indium leukocyte studies (for quantification of intestinal inflammation). Twenty-six men with AIDS had a dual radioisotopic ileal function test (whole body retention of tauro 23-[75Se]-selena 25-homocholic acid and 58cobalt-labelled cyanocobalamine), and 17 underwent ileocolonoscopy with terminal ileal biopsy. RESULTS: Well, HIV-infected, subjects had normal intestinal absorption-permeability, but both functions were impaired upon the development of AIDS. The median faecal excretion of 111indium in well patients (0.66%) did not differ significantly (P > 0.5) from controls (0.46%), but subjects with AIDS who were well or who had diarrhoea had significant (P < 0.005) intestinal inflammation (1.33% and 2.18%, respectively). The median 7-day retention of tauro 23-[75Se]-selena 25-homocholic acid in well patients with AIDS (38.9%) did not differ significantly (P > 0.2) from controls (39.3%), whereas the absorption of 58cobalt-labelled cyanocobalamine was significantly (P < 0.05) lower than controls (32.1% and 59.4%). Patients with AIDS-diarrhoea had significant (P < 0.001) malabsorption of both the bile acid (7.7%) and vitamin B12 (8.9%) which was more severe than in Crohn's ileitis (14.2% and 30.3%, respectively). Morphometric analyses of ileal biopsies were unremarkable in AIDS. CONCLUSIONS: These studies demonstrate a low-grade enteropathy in patients with AIDS, severe ileal malabsorption in patients with AIDS diarrhoea and relatively minor ileal morphologic changes. Malabsorption of bile acids may play a pathogenic role in patients with AIDS and diarrhoea.

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BACKGROUND/AIM: The reliability of a quantitative method for the non-invasive assessment of intestinal disaccharide hydrolysis was assessed. METHODS: Differential excretion of intact disaccharide, expressed as ratios of lactulose to appropriate hydrolysable disaccharides in urine collected following combined ingestion, has been investigated in healthy volunteers with drug induced alpha-glucosidase inhibition, in subjects with primary hypolactasia, and patients with coeliac disease. RESULTS: Oral administration of the alpha-glucosidase inhibitor 'Acarbose' (BAY g 5421, 200 mg) together with sucrose and lactulose increased the urinary sucrose/lactulose excretion ratios (% dose/10 h) fivefold. The effect was quantitatively reproducible, a higher dose of 'Acarbose' (500 mg) increasing the excretion ratio to about 1.0 indicating complete inhibition of intestinal sucrase activity. The suitability of the method for measuring differences in dose/response and duration of action was assessed by comparing three different alpha-glucosidase inhibitors (BAY g 5421, BAY m 1099, and BAY o 1248) and found to be satisfactory. Subjects with primary adult hypolactasia had urine lactose/lactulose excretion ratios raised to values indicating reduced rather than complete absence of lactase activity whereas sucrose/lactulose ratios were not significantly affected. 'Whole' intestinal disaccharidase activity assessed by this method demonstrated impairment of lactase, sucrase, and isomaltase in eight, one, and seven, respectively, of 20 patients with coeliac disease. By contrast in vitro assay of jejunal biopsy tissue indicated pan-disaccharidase deficiency in all but five of these patients. This shows the importance of distinguishing between 'local' and 'whole' intestinal performance. CONCLUSIONS: Differential urinary excretion of ingested disaccharides provides a reliable, quantitative, and non-invasive technique for assessing profiles of intestinal disaccharidase activity.

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OBJECTIVE: To assess gastrointestinal permeability and functional absorptive capacity in patients with sepsis. DESIGN: Case control study to analyze gastrointestinal permeability and functional absorptive capacity of septic patients by differential saccharide absorption (from an oral test solution) and excretion. SETTING: The intensive Therapy Unit of St. Thomas' Hospital, London, UK. PATIENTS: Twenty patients with a mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of 18.4 who were admitted to the intensive care unit with a diagnosis of sepsis. All patients were on enteral feeding. Patients with abdominal pathology were excluded. INTERVENTIONS: An oral test solution containing 5 g of lactulose, 1 g of L-rhamnose, 0.5 g of D-xylose, and 0.2 g of 3-O-methyl-D-glucose dissolved in water to a final volume of 100 mL was administered to patients and controls. Urine was collected for 5 hrs starting immediately after administration of the test solution and the saccharide content of the urine was estimated and expressed as a percentage recovery of the oral test solution. MEASUREMENTS AND MAIN RESULTS: Septic patients had increased lactulose/L-rhamnose urine excretion ratios (0.23 +/- 0.19) compared with control subjects (0.03 +/- 0.01, p < .001), consistent with increased gastrointestinal permeability in sepsis. Septic patients had decreased L-rhamnose/3-O-methyl-D-glucose urine excretion ratios (0.14 +/- 0.07) compared with normal controls (0.28 +/- 0.08, p < .001), consistent with decreased gastrointestinal functional absorptive capacity in sepsis. CONCLUSIONS: Patients with acute sepsis exhibit increased gastrointestinal permeability and decreased gastrointestinal functional absorptive capacity in comparison with healthy control subjects. These abnormalities may contribute to the pathophysiology of sepsis.

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Intestinal function is poorly defined in patients with HIV infection. Absorptive capacity and intestinal permeability were assessed using 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in 88 HIV infected patients and the findings were correlated with the degree of immunosuppression (CD4 counts), diarrhoea, wasting, intestinal pathogen status, and histomorphometric analysis of jejunal biopsy samples. Malabsorption of 3-O-methyl-D-glucose and D-xylose was prevalent in all groups of patients with AIDS but not in asymptomatic, well patients with HIV. Malabsorption correlated significantly (r = 0.34-0.56, p < 0.005) with the degree of immune suppression and with body mass index. Increased intestinal permeability was found in all subgroups of patients. The changes in absorption-permeability were of comparable severity to those found in patients with untreated coeliac disease. Jejunal histology, however, showed only mild changes in the villus height/crypt depth ratio as compared with subtotal villus atrophy in coeliac disease. Malabsorption and increased intestinal permeability are common in AIDS patients. Malabsorption, which has nutritional implications, relates more to immune suppression than jejunal morphological changes.

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BACKGROUND: The relationship between disaccharidase activity, progression of human immunodeficiency virus (HIV) disease, and diarrhoea and weight loss was investigated. METHODS: Forty-six HIV-positive patients ingested a solution of lactose, palatinose, sucrose, and lactulose after 24 h of dietary exclusion and overnight fasting, after which urine was collected for 10 h. Urinary disaccharide (activity) ratios-lactose/lactulose (L/LL), palatinose/lactulose (P/LL), and sucrose/lactulose (S/LL)-were measured by thin-layer chromatography. RESULTS: There was a significant decrease in disaccharidase activity (L/LL, P/LL, and S/LL) with advancing clinical stage of HIV disease (p < 0.05, Wilcoxon rank sum test) as well as decreasing CD4 count (p < 0.05, Spearman correlation). Patients with weight loss/diarrhoea also had significantly (p < 0.05) decreased disaccharidase activity compared with control but not as compared with AIDS patients. Anti-retroviral therapy did not influence disaccharidase activity. CONCLUSION: Impairment of disaccharidase activity occurs with advancing HIV disease, but its role in HIV patients with weight loss and diarrhoea remains to be determined.

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BACKGROUND: We have previously shown that small oral doses of poorly absorbed solute can significantly reduce absorption of test sugars in normal volunteers. To confirm these results and investigate the underlying mechanism, the effects of lactulose on absorption of three test sugars in subjects with ileostomies were studied. METHODS: Ten fasted subjects with ileostomies ingested an isosmolar test solution containing 2.5 g 3-O-methyl-D-glucose, 5.0 g D-xylose, 1.0 g L-rhamnose, and 50 microCi 51Cr-labelled ethylenediaminetetraacetic acid together with a blue dye transit marker. Urine was collected for time periods of 0-5 h and 5-24 h, to measure excretion of absorbed sugars, and ileostomy effluent was saved from 0-5 h and from 5 h until blue dye transit marker was no longer present, to measure small-bowel output of unabsorbed sugars. After 1 week the test was repeated, including 5 g lactulose in the test solution. RESULTS: Inclusion of lactulose in the test solution significantly reduced the 5 h and 24 h urine excretion of L-rhamnose and D-xylose but not that of 3-O-methyl-D-glucose and increased 0- to 5-h and total ileostomy output of L-rhamnose and D-xylose but not of 3-O-methyl-D-glucose. The presence of lactulose also reduced the time for first appearance of the blue dye transit marker in the effluent and increased effluent volume together with output of electrolyte. CONCLUSION: Poorly absorbed solute reduces intestinal absorption by retention of fluid and electrolyte, with subsequent intraluminal dilution and acceleration of transit.

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Total parenteral nutrition is used for nutritional support in patients undergoing orthotopic liver transplantation but is associated with complications. We compared the efficacy and tolerability of early enteral feeding with total parenteral nutrition after liver transplantation. 24 patients were studied: 14 received enteral feeding and 10 total parenteral nutrition. A double-lumen enteral tube was used to deliver the feed directly into the jejunum with the second lumen of the tube being used for gastric aspiration. Enteral feeding was started post-operatively within 18 h, was well-tolerated, and of comparable efficacy to total parenteral nutrition. The median number of days for patients to start eating (4) and to achieve 70% of estimated requirements orally (5) did not differ significantly between the two groups. Mid-arm circumference, triceps skinfold thickness, and biceps skinfold thickness were, by comparison with pre-operative values, maintained on the tenth postoperative day in both groups. Early postoperative absorptive capacity, as assessed by a combined carbohydrate test, was reduced significantly in both groups but insufficiently to be of nutritional concern. Intestinal mucosal integrity, as assessed by an intestinal permeability test, was maintained throughout. We conclude that the practical aspects of enteral feeding after liver transplantation are surmountable and that enteral feeding is as effective at maintaining nutritional status as total parenteral nutrition, and has potential benefits in terms of reduced complications and costs.

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BACKGROUND: Controversy surrounds the issue of intestinal permeability in patients with coeliac disease, polyethylene glycol 400 indicating reduced and di-/mono-saccharide urine excretion ratios and 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) indicating increased permeability. METHODS: We assessed the suitability of polyethylene glycol 400, L-rhamnose, lactulose, and 51Cr-EDTA as markers of intestinal permeability by assessing urine excretions after simultaneous intravenous instillation of these markers and after oral administration in normals and patients with coeliac disease. RESULTS: After intravenous administration the 24-h urine excretion of polyethylene glycol 400, L-rhamnose, lactulose, and 51Cr-EDTA was 40%, 72%, 93%, and 97%, respectively. There was no significant difference between controls and patients with coeliac disease. Oral administration of the markers in an iso- and hyper-osmolar test solution demonstrates reduced permeation due to an osmotic retention effect of lactulose. In contrast, hyperosmolar glycerol increases permeation of all markers except L-rhamnose. Timing of urines and altering osmolarity is important for the behavior of individual markers but does not enhance the discrimination between controls and patients when the differential urine excretion of lactulose/L-rhamnose is used. The sensitivity of the urine excretion ratio of lactulose/L-rhamnose was comparable to that of 51Cr-EDTA used by itself. Whereas lactulose/L-rhamnose and 51Cr-EDTA showed increased intestinal permeability in coeliac disease, the permeation of polyethylene glycol was reduced. Permeation of the markers did not correlate significantly with jejunal histology. CONCLUSIONS: Correlations of marker permeation rates with test dose osmolarity in controls and patients with coeliac disease shows a variable lack of conformity, suggesting that the markers may permeate the intestine by different routes, which are affected to a different extent in coeliac disease.

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To investigate the effects of high altitude on intestinal function, the absorption and permeation of nonmetabolizable carbohydrates were measured in 14 volunteers (median age 21 yr, range 19-37 yr) at sea level in Oxford, UK; at 1,050 m in Nepal; at 5,570 m after 5 days at > 5,500 m; and at 5,730 m after 11 days at > 5,500 m. Body weight decreased 5.7 +/- 1.19 kg from sea level to 5,570 m (P < 0.001 by paired t test) despite 72-h dietary records showing no change in energy intake. Absorption of carbohydrates by mediated transport was measured by urinary xylose and 3-O-methyl-D-glucose excretion. Xylose excretion (%oral dose) decreased from 31.4 +/- 4.5% to 20.7 +/- 4.5% (P < 0.001) and 3-O-methyl-D-glucose excretion decreased from 39.7 +/- 6.1 to 33.7 +/- 7.0% (P = 0.003) from sea level to 5,730 m. Monosaccharide permeation measured by L-rhamnose excretion decreased from 11.3 +/- 2.5 to 6.2 +/- 2.0% (P = 0.001). Intestinal permeability, a measure of barrier function (ratio of lactulose to L-rhamnose), increased from 0.036 +/- 0.014 at sea level to 0.084 +/- 0.042 at 1,050 m (P = 0.006), possibly due to infective enteropathy after arrival in Nepal, but reverted to normal (0.045 +/- 0.013; P = 0.062) at 5,730 m. Absorption of all carbohydrates returned to normal after return to the UK. This study showed that a decrease in mediated (D-xylose or 3-O-methyl-D-glucose) and diffusional (L-rhamnose) monosaccharide absorption occurs at high altitude but that intestinal permeability at 5,730 m is unchanged.

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BACKGROUND/AIMS: Mean arterial pressure is reduced during hypothermic cardiopulmonary bypass. The aim of this study was to assess whether this was associated with intestinal hypoperfusion and whether it affected intestinal absorption and permeability. METHODS: Twenty-six patients undergoing coronary artery bypass grafting underwent an intestinal absorption-permeability test involving ingestion of 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose. Ingestion took place 2 days before, within 3 hours, and 5 days after hypothermic cardiopulmonary bypass. Hemodynamic parameters and gastric mucosal laser Doppler blood flow were measured perioperatively in eight patients. RESULTS: Hypothermic (28 degrees C), nonpulsatile cardiopulmonary bypass resulted in a 25% reduction in mean blood pressure, 10% reduction in cardiac index, and a 46% reduction in gastric mucosal laser Doppler blood flow. There was 85.4%, 85.5%, and 73.6% reduction (P < 0.01) in active (3-O-methyl-D-glucose) and passive (D-xylose) carrier-mediated transport and passive, nonmediated transcellular (L-rhamnose) transport in the immediate postoperative period, respectively. The differential urine excretion of lactulose/L-rhamnose increased sixfold. All parameters returned to control levels by the fifth postoperative day. CONCLUSIONS: Cardiopulmonary bypass, while maintaining generally acceptable levels of hemodynamic performance, is associated with significant intestinal hypoperfusion and malabsorption of monosaccharides, which may have implications for enteral drug treatment in the immediate postoperative period.

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The relationships among intestinal permeability, advancing human immunodeficiency virus (HIV) infection, and the presence of diarrhoea or weight loss were investigated in 51 HIV patients and 20 healthy controls. Ten patients with untreated coeliac disease were also investigated for comparison. Fasting subjects drank an isosmolar test solution containing D-xylose, lactulose (LL), L-rhamnose (R) and 3-O-methyl-D-glucose. Urine was collected for 5 h, test sugar content being subsequently measured by thin-layer chromatography for the dosing sugars. Intestinal permeability (LL/R excretion ratio) and recovery of D-xylose and 3-O-methyl-D-glucose in urine were abnormal in patients with HIV disease, and especially those with diarrhoea, as they were in coeliac disease. Patients with coeliac disease and HIV disease, especially when diarrhoea and/or weight loss were present, had significantly reduced 5-h excretion of L-rhamnose, D-xylose, and 3-O-methyl-D-glucose. These data indicate that abnormal permeability and reduced intestinal absorption capacity are common in HIV patients, occur at all stages of HIV disease, especially in the presence of diarrhoea, and, with the exception of lactulose permeation, are relatively similar to the alterations seen in coeliac disease.

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We measured small intestinal permeability to lactulose and rhamnose in 18 healthy children and in 15 children with atopic eczema, before and after a 14-day elimination diet. The children with atopic eczema had higher initial urinary lactulose/rhamnose ratios than the controls. After dietary restriction, there was no overall change in permeability. Dietary therapy did however result in a large reduction in permeability in three of the nine children whose skin disease was improved, but a statistically significant decrease in permeability was not observed in the diet-responsive group as a whole. Larger studies would be required to confirm that dietary restrictions can reduce intestinal permeability in some children with atopic eczema.

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In normal adults intestinal permeation of ingested 51Cr-ethylenediaminetetraacetic acid (EDTA) is greater than that of lactulose. This difference is abolished in patients with ileostomies, suggesting that it results from colonic permeation of 51Cr-EDTA, which, unlike lactulose, resists bacterial degradation. To investigate the effect of an increase in colonic permeability on absorption of the two molecules, lactulose (5 g) and 51Cr-EDTA (50 microCi) were given orally in isosmolar solution to 11 patients with colitis, and their 24-h urinary excretion measured. By comparison the effect of an increase in small-intestinal permeability induced by ingestion of a hyperosmolar solution (4240 mosm/l) was measured in 10 healthy adults. Hyperosmolar stress increased the 24-h urinary excretion of 51Cr-EDTA above the normal mean + 2 standard deviations (3.31%) in all 10 healthy subjects, and in all of these excretion of lactulose was also increased (greater than 1.06%). In contrast, although seven colitics had a urinary excretion of 51Cr-EDTA above the normal mean + 2 SD, in only two of these patients was recovery of lactulose increased. This suggests that simultaneous administration of lactulose and 51Cr-EDTA may enable permeability changes affecting the colon alone to be distinguished from those involving the small intestine.

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Nonsteroidal anti-inflammatory drug (NSAID)-induced increased intestinal permeability appears to be a prerequisite for NSAID enteropathy. It has been suggested that early metabolic events leading to the permeability changes may involve inhibition of glycolysis and the tricarboxylic acid cycle, in which case the coadministration of glucose and citrate (the substrates for these metabolic pathways) with indomethacin may afford some protection. The present study, using a combined intestinal absorption-permeability test including 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and [51Cr]ethylene-diaminetetraacetic acid (EDTA) as test probes and the differential urine excretion ratio of [51Cr]-EDTA/L-rhamnose, showed that indomethacin (50 + 75 mg) increased intestinal permeability. A formulation of indomethacin containing 15 mg glucose and 15 mg citrate to each milligram of indomethacin did not increase intestinal permeability significantly above baseline values. When given alone with indomethacin, neither glucose nor citrate (45 mg to each milligram of indomethacin) had any protective effects. Pharmokinetic studies showed that the effects of glucose and citrate cannot be explained on the basis of altered drug absorption. These results suggest a new approach to reducing the small intestinal side effects of NSAIDs.

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