Correlation of lactulose-to-mannitol ratios in plasma and urine for intestinal permeability assessment in pigs.

OBJECTIVE: The lactulose-to-mannitol ratio test is a test to assess the disorders associated with gut permeability. The test requires an oral administration of the mixture of lactulose and mannitol and urine collection. The urinary ratio of lactulose to mannitol is an indicator of intestinal permeability. Due to the complexity of urine collection in animal studies, plasma exposure ratios of lactulose to mannitol compared to their urinary concentration ratios were evaluated following an oral administration of the sugar mixture in pigs. ANIMALS: 10 pigs were orally dosed with a solution of lactulose and mannitol mixture. PROCEDURES: Plasma samples were collected at predose, 10 and 30 minutes and 2, 4, and 6 hours postdosing, and cumulated urinary samples were collected at 6 hours for liquid chromatography-mass spectrometry analysis. The ratios of pharmacokinetic parameters of lactulose to mannitol and the plasma sugar ratios at a single time point or the mean values of several time points were compared to their urinary sugar ratios. RESULTS: The results revealed that the lactulose-to-mannitol ratios of AUC0-6h, AUCextrap, and Cmax were correlated to the urinary sugar ratios, and the plasma sugar ratios of a single time point at 2, 4, or 6 hours and the mean values of those time points were also appropriate to replace their urinary ratios in pigs. CLINICAL RELEVANCE: Following an oral administration of lactulose and mannitol mixture, blood collection, and assay can be an option for assessing intestinal permeability, especially in animal studies.

Semiquantitative assessment of breath hydrogen testing.

BACKGROUND AND AIM: A major use of breath hydrogen testing is to assess absorptive capacity for sugars to assist dietary design for management of gut symptoms. Qualitative reporting takes no account of the vigor of hydrogen response and provides little insight into degrees of malabsorption. This study aimed to describe a semiquantitative reporting method and to compare results with those reported qualitatively. METHODS: In consecutive Caucasian patients with Crohn's disease (n = 87), ulcerative colitis (59), functional gastrointestinal disorders (FGID) (162), and healthy controls (76), area under the curve was calculated for lactulose (15 g). This was compared with that for lactose (50 g) and fructose (35 g). Degree of malabsorption was categorized into arbitrary groups. RESULTS: Semiquantitative results for ≥ 30% (designated "convincing") malabsorption was most similar to those using a qualitative cutoff value of 20 ppm, but in 38% and 21% of patients, the classification of malabsorption (nil or clinically significant) changed for fructose and lactose, respectively. Using a cutoff of 10 ppm, 49% and 5% were classified differently. Crohn's disease had a higher prevalence (42%) of convincing fructose malabsorption than controls (24%) or patients with FGID (33%) (P < 0.02). Highest prevalence of convincing lactose malabsorption (38%) was in ulcerative colitis, greater than controls (18%) and FGID (18%) (P < 0.02). CONCLUSIONS: Semiquantitative assessment provides different results with different clinical implications in more than one third of patients, but disease-related alterations in prevalence are similar to those defined qualitatively. This method may be preferable because it lessens the confounding influence of the vigor of the hydrogen response.

Assessment of intestinal permeability using sugar probes: influence of urinary volume.

BACKGROUND: As the accuracy of the "Sugar Test" is currently debated, this study was conducted to focus on how urine volumes may impact the test results. METHODS: Fifty-five subjects, 23 healthy and 32 with Irritable Bowel Syndrome (IBS), were enrolled. Lactulose and D-mannitol dissolved in water were administered to all the participating subjects; the urine excreted was collected and the total urine volume was measured. The urine samples were analyzed by High Performance Liquid Chromatography (HPLC). The results were expressed as percentage of urine recovery of lactulose and D-mannitol and lactulose/D-mannitol ratio (LMR). RESULTS: All subjects were divided into two groups: subjects with urine volume < 500 mL and subjects with urine volume > or = 500 mL. Urine analysis showed that the mean LMR was significantly lower in subjects with urine volume > or = 500 mL than in subjects with urine volume < 500 mL (0.02 +/- 0.02 vs 0.04 +/- 0.04; p < 0.05). A significant increase in D-mannitol recovery was found to be associated with greater urine volumes (p < 0.001). CONCLUSIONS: The urine volume may influence urinary excretion of sugar probes. Intake of liquids should therefore be carefully monitored before and during the test and the volume of urine produced over the period of collection should be precisely measured.

Experimental assessment of chemotherapy-induced early intestinal damage in colon cancer the lactulose-mannitol permeability test.

AIMS AND BACKGROUND: Although chemotherapy plays an important role in the management and cure of cancer, it has undesiderable side effects mostly affecting the bone marrow and gastrointestinal tract, which greatly limit patient compliance and treatment efficacy. METHODS: The lactulose-mannitol test was used to assess intestinal mucosa damage 48 hours after the end of the first adjuvant chemotherapy cycle with 5-fluorouracil (5-FU) and levamisole in 12 patients with colon cancer. Fifteen age- and sex-matched subjects were studied as controls. The excreted amount of lactulose and mannitol was expressed as the percentage of the administered doses recovered in the urine as well as their ratio. RESULTS: The percent urinary recovery of lactulose was significantly (P < 0.001) higher in colon cancer patients (1.1 +/- 0.5%) than in the control group (0.3 +/- 0.03%), whereas the mannitol recovery was only slightly reduced in the former. As a result, the lactulose/mannitol excretion ratio was significantly (P < 0.001) higher in colon cancer patients (0.07 +/- 0.03) than in the control group (0.01 +/- 0.01). CONCLUSIONS: As assessed by the lactulose-mannitol test, the combined chemotherapy regimen with 5-FU and levamisole affects mainly the barrier function of the intestinal mucosa rather than its absorption capacity. The toxic effect seems to be attributable to the 5-FU molecule rather than to levamisole. The lactulose-mannitol test is a simple, safe and reliable tool to evaluate chemotherapy-induced early damage to the intestinal epithelium, in particular when new kinds of substances are being administered. Its use in clinical practice seems appropriate to establish the correct timing of drug administration, thereby enhancing treatment efficacy and improving patient compliance.

Assessment of intestinal permeability changes induced by nonsteroidal anti-inflammatory drugs in the rat.

Intestinal permeability was investigated as an alternative to intestinal ulceration for measuring nonsteroidal anti-inflammatory drug (NSAID) gut damage in the rat and developed as a method for routine measurement. NSAID dose-response curves produced using the two indices of damage showed that intestinal permeability is as sensitive and reproducible as ulceration, although changes could not be detected before visible ulceration occurred. Lactulose, [51Cr]-EDTA and [14C]-carboxyinulin were compared as possible in vivo markers of rat intestinal permeability. Measurement of [51Cr]-EDTA permeation was found to be the most sensitive and reproducible method. Dose-response curves produced by measuring [51Cr]-EDTA permeation were used to compare the potency of the two NSAIDs piroxicam and (S+) ibuprofen; piroxicam was found to be 10 times more potent in increasing intestinal permeability than (S+)-ibuprofen. These studies show that intestinal permeability measurement is a useful alternative to other methods of assessing NSAID adverse effect and is easily and rapidly performed.

Analysis of multiple sugar probes in urine and plasma by high-performance anion-exchange chromatography with pulsed electrochemical detection. Application in the assessment of intestinal permeability in human immunodeficiency virus infection.

Mannitol, 3-O-methylglucose and lactulose administered orally are used to investigate small intestinal absorption pathways and mucosal integrity. Current methods of analysis include thin-layer chromatography, gas chromatography (GC) and enzymatic analysis, which require separate estimation of mono- and disaccharides and for GC, prior derivatization. We describe a high-pressure anion-exchange chromatographic method coupled with pulsed electrochemical detection allowing simultaneous measurement of all three sugars and its clinical application in monitoring intestinal damage in human immunodeficiency virus (HIV) infection. Sample preparation is simple and fast. All sugars are resolved within 10 min. Mean recovery is 93.3% for all sugars and the overall relative standard deviation is 4.2%. Intestinal permeability (lactulose/mannitol ratio) rises with disease progression to AIDS, indicating mucosal damage. The greatest increase in permeability is associated with chronic diarrhoea. The method is an ideal non-invasive test to assess gut mucosal damage in HIV infection.