5-aminosalicylic acid release from a new controlled-release mesalazine formulation during gastrointestinal transit in healthy volunteers.

BACKGROUND: Mesalazine (5-aminosalicylic acid, 5-ASA) containing formulations represent a cornerstone in the treatment of inflammatory bowel diseases. A novel formulation with an Eudragit L/S mixture coating has been developed to provide selective release of 5-ASA to the ileo-caecal region and the colon. AIM: To determine the release of 5-ASA during the gastrointestinal transit. METHODS: A single oral dose of mesalazine EC 500 mg gastroresistant tablets (Asamax) was administered to eight healthy male volunteers. Gastrointestinal transit and tablet disintegration were monitored by scintigraphy. 5-ASA release was verified by assessing plasma pharmacokinetics. RESULTS: Initial tablet disintegration was observed 5.65 +/- 0.86 h after dosing, corresponding to the detection of 5-ASA in plasma. This occurred in the ileo-caecal region in three subjects and the ascending colon in the remaining five. The relative percentage of 5-ASA absorption was more pronounced in the ascending colon (41 +/- 27.4%) than the ileo-caecal region (6.6 +/- 9.2%). CONCLUSION: This mesalazine EC gastroresistant tablets release locally active 5-ASA specifically in the ileo-caecal region and the ascending colon.

Gastrointestinal transit and 5-ASA release from a new mesalazine extended-release formulation.

BACKGROUND: Mesalazine (5-aminosalicylic acid, 5-ASA)-containing formulations represent a cornerstone in the treatment of inflammatory bowel diseases. Recently, a new formulation has been developed to provide selective and more homogeneous release of 5-ASA compared to traditional systems. METHODS: In a first study, gastrointestinal transit was followed by gamma-scintigraphy after single-dose application of tablets containing 1200 mg mesalazine to 12 healthy male volunteers. 5-ASA release was verified by the assessment of plasma pharmacokinetics. In a second, 7-day, multiple-dose study, the steady state plasma pharmacokinetics, urinary excretion and safety profile were characterized after twice-daily tablet administration to 12 healthy volunteers. RESULTS: Tablet erosion started after 6.9 +/- 1.1 h in the ascending or transverse colon. Radioactivity spread homogeneously throughout the colon, indicating the sustained release of active 5-ASA. Plasma kinetics indicated an earlier initial absorption of 5-ASA, i.e. during transit of the small intestine and ileum. Mean Cmax values (350.6 +/- 322.6 ng/mL) were observed during location in the ileo-caecal region. The mean relative absorption of 5-ASA was 19.9 +/- 18.2% in the small intestine and ileum and 80.1 +/- 18.2% in the colon. CONCLUSIONS: The administration of the new mesalazine formulation was well tolerated, and 5-ASA was continuously released along the whole colon, a favourable prerequisite for the therapy of distally located inflammatory bowel disease.

Results and conclusions of the Austrian radon mitigation project 'SARAH'.

The Austrian radon mitigation joint research project SARAH (supported by the Austrian Ministry of Economy and the Government of Upper Austria), a 2-year follow-up study of the Austrian National Radon Project (ONRAP), was started in 1996. The objectives of the research project were to find simple, cost-effective experimental methods for the characterisation of the radon situation in dwellings and to evaluate technically and economically the implementation of state of the art remedial actions for Austrian house types. After an intercomparison exercise of the assigned radon measuring instruments and detectors five houses were closely examined in regions with elevated radon levels in the federal state of Upper Austria. In this research work for the first time an extended Blower-Door method (which is conventionally used for determining the tightness of buildings) was successfully applied to radon diagnosis of buildings. In this paper the methods used for the radon diagnosis, the applied mitigation measures and the related technical and economical aspects are discussed. In conclusion of the results of this project a common strategy for solving the radon problem in Austria in the future is presented briefly.

Gastrointestinal transit, release and plasma pharmacokinetics of a new oral budesonide formulation.

AIMS: The aims of the study were to: (1) evaluate the gastrointestinal transit, release and absorption of budesonide from tablets with a new multimatrix formulation (MMX) designed to release the drug throughout the whole colon, and (2) assess the influence of food on budesonide bioavailability. METHODS: Two phase I studies, each comprising 12 healthy males, were performed. Gastrointestinal transit of (153)Sm-labelled tablets containing 9 mg budesonide was evaluated by means of pharmaco-scintigraphy. The effect of food was tested by comparing plasma pharmacokinetics after intake of a high fat and high calorie breakfast with fasting controls. RESULTS: (153)Sm-labelled tablets reached the ascending colon after a mean +/- SD 9.8 +/- 6.9 h. Initial tablet disintegration was observed in the ileum in 42% and the ascending and transverse colon in 33% of subjects. Ninety-six per cent of the dose was absorbed into the systemic circulation during passage through the whole colon including the sigmoid. Food significantly decreased C(max) values from 1429 +/- 1014 to 1040 +/- 601 pg mL(-1) (P = 0.028) and AUC values from 14 814 +/- 11 254 to 13 486 +/- 9369 pg h(-1) mL(-1) (P = 0.008). Mean residence time and t(max) increased by 12-29%. There was no drug accumulation after 1 week of once daily oral administration of budesomide. CONCLUSIONS: MMX-budesonide tablets appear suitable for targeted colonic drug delivery. Transit parameters and low systemic bioavailability warrant further studies with the new formulation.

[SI-units in radiotherapy and radiation protection--an addendum (author's transl)]. / SI-Einheiten in Strahlentherapie und Strahlenschutz--ein Nachtrag.

As an extension of a recent paper, this addendum conversion tables between the new SI-unit Sievert (Sv) for the dose equivalent and the unit Rem (rem) used previously, as well as the relations of the corresponding dose rates.

[SI-units in radiotherapy and radiation protection (author's transl)]. / SI-Einheiten in Strahlentherapie und Stahlenschutz

A review is given about SI units as they will be used in future in radiotherapy and health physics. The paper includes conversion tables for the units used in these fields and presents some somments on possible difficulties by using these units in practical work.

Licencing of medical x-ray equipment in 1899: background and procedure.

The full text of probably the first worldwide licencing procedure for x-ray equipment has now become available. The document is dated 27 December 1898 and is a formal request from one authority to another to look into what was going on in an institute which called itself Institut für Röntgenuntersuchungen. In response to this, a committee considering both formal and scientific aspects of licencing was founded. This paper shows in brief the scientific background on the detrimental radiation effects available at the turn of the century, and reports on the decisions made by the authorities.