PubMed · 7255535
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
T N Tozer. 1981. Concepts basic to pharmacokinetics.. https://doi.org/10.1016/0163-7258(81)90077-2
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
BACKGROUND: Sufficient intraluminal concentrations of 5-aminosalicylic acid (ASA) within inflamed regions of the intestine are required for therapeutic efficacy in inflammatory bowel disease. Various oral delayed release preparations have been developed to ensure that 5-ASA is set free in those parts of the gut, which are most frequently affected. However, resulting intraluminal concentrations within the small bowel are unknown. Therefore, we determined and compared 5-ASA release within different segments of the small bowel from an Eudragit L coated 5-ASA preparation (Salofalk) and from an ethylcellulose coated microsphere preparation (Pentasa). METHODS: Twelve healthy subjects were intubated with an oro-ileal multilumen-tube for marker perfusion, duodenal, jejunal and ileal aspiration of chyme and intestinal manometry. Each subject received 500 mg 5-ASA (Salofalk, n = 6, or Pentasa, n = 6) together with a semiliquid test meal. Intestinal aspirates, blood and urine samples were obtained in regular intervals for 7 to 10 hours and were analysed for 5-ASA and its main metabolite acetyl-5-ASA by HPLC. RESULTS: With Salofalk, gastric emptying of 5-ASA did not take place in the digestive, but in the subsequent interdigestive period. Luminal delivery of 5-ASA and acetyl-5-ASA increased from the duodenum (3% of dose) to the ileum (30% of dose). 10% of the dose administered were excreted in urine and about 90% reached the colon unreleased or solubilised. By contrast, with Pentasa, 5-ASA was delivered to the duodenum together with the test meal and released continuously throughout the small intestine (about 20% of dose solubilised at each intestinal site). Only 3.5% of the dose administered were excreted in urine. Deliver of 5-ASA to the colon was equal to Salofalk. CONCLUSIONS: From both preparations, considerable amounts of 5-ASA are released during small intestinal transit thus explaining therapeutic efficacy in small intestinal Crohn's disease. Because of specific release patterns, Salofalk may be of use especially in terminal ileal disease, where as patients with extensive small intestinal disease including the proximal small intestine might benefit from Pentasa.
In patients with malignancies and immune disorders expressing Tac (alpha chain of the interleukin 2 receptor; CD25), physiologic shedding of this receptor may lead to high blood levels of the soluble form (sTac). This system was used to model the interaction of soluble antigen with antibody in therapeutic settings and to develop rational principles to optimize the delivery of antibody to tumor target cells. First, we confirmed that sTac in vivo can block anti-Tac binding sites and diminish antibody binding to Tac+ cells. Second, the bioactivity of antibody in vivo correlated directly with the amount of antibody infused and inversely with the sTac concentration. Third, bindability of antibody declined in the hours and days after anti-Tac infusion in patients. Finally, tumor targeting was achieved even in the presence of excess sTac, demonstrating a partition of antibody between soluble and cell-bound antigen. A role is proposed for the Brambell receptor (FcRB) to delay saturation of human or chimeric antibodies via differential catabolism of antigen-antibody complexes. Principles are developed for predicting activity of administered antibody in the presence of soluble antigen to assist in dose selection in passive, radioimmuno and immunotoxin therapies.
For centuries the city of Falun in central Sweden has been an important industrial region of copper mining, producing sulphuric acid and paint pigment. The mining and chemical industries have generated vast amounts of wastes which have been deposited around the areas. A large part of the city is now built on the wastes. In the last two decades, significant amounts of work on the waste management have been conducted. Previous investigations showed that the soils of the urban areas have been contaminated by the wastes with a rather high level of lead (Pb). What is the speciation of soil-Pb? How does the Pb reach the biosphere? This paper gives answers toward these environmental problems. This study investigates the distribution of Pb in the urban soils by means of chemical and mineralogical methods the quantity and quality of the fallout particles; and traces the potential sources of contamination. The data indicate that in Falun urban soil-Pb speciation, many mainly be associated with some mineral phases, e.g. Fe and Mn oxides, sulphides, Pb-carbonates, as well as retained by organic matters and clay minerals. The concentrations of water soluble Pb are very low. Because of the properties of the Pb-bearing phases, the high concentrations of soil-Pb in the urban area are not likely to have a significant affect on the blood-Pb levels of pre-school children living in the urban areas. Lead and arsenic are found to be associated with iron oxides in the fallout particles collected in the areas. These fine grained particles may have been distributed through wind-related transportation from the industrial wastes dumped in the areas.