betadex and Gastrointestinal-Hemorrhage

Piroxicam-beta-cyclodextrin (PBC), a complex of piroxicam with beta-cyclodextrin, was developed with the aim of improving the hydrosolubility and bioavailability of piroxicam. The complex is more rapidly absorbed, with a consequent reduction in the time of contact of piroxicam with the gastric and duodenal mucosa. It is hoped that the shorter contact time might reduce the local toxicity of piroxicam, but it is also possible that transiently higher local concentrations of the drug might worsen the injury to the gastro-duodenal mucosa. Four studies have been conducted in healthy volunteers in order to investigate the effects of PBC on the gastro-intestinal tract. In 3 of these trials, all of similar design, PBC (containing 20 mg of piroxicam) was compared with piroxicam 20mg and placebo given once daily with assessment of faecal blood loss using the 51Cr-labelled red-cell technique, and endoscopic appearance of gastroduodenal mucosa before and after 28 consecutive days of treatment. One study showed a significant difference in respect of faecal blood loss towards the end of the 4-week study period favouring PBC over piroxicam, while the 2 others showed comparable but non-significant trends in favour of PBC. In a fourth study, 32 non-patient volunteers received either piroxicam 20mg once daily; PBC 20mg equivalence; indomethacin 50mg twice daily; or placebo. The treatment was given double blind for 14 days. Endoscopy was performed and gastric potential differences were measured by neutral observers before and at the end of treatment. There were no significant differences in the endoscopic scores between the active treatment groups. The gastric potential difference showed greater changes with indomethacin and piroxicam than with placebo and PBC.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Controlled Clinical Trials as Topic; Cyclodextrins; Digestive System; Double-Blind Method; Drug Combinations; Female; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Indomethacin; Male; Middle Aged; Piroxicam

Thirty-six healthy men aged 20-31 years took part in a randomized, double-blind, double-dummy, parallel-group study to compare the effects of repeated doses of piroxicam-beta-cyclodextrin, piroxicam and placebo on faecal blood loss and the endoscopic appearances of gastric and duodenal mucosa. After an initial endoscopy, subjects received on day 0 autologous erythrocytes labelled with 51Cr. Complete daily faecal collections were then made from days 6 to 12. From days 13 to 40, subjects received daily by mouth either piroxicam-beta-cyclodextrin (containing 20 mg piroxicam), piroxicam 20 mg, or placebo. Complete faecal collections were made daily from days 13 to 41; blood samples for red-cell 51Cr activity were taken weekly. Endoscopy was repeated 16-20 h after the last dose of medication. Faecal blood loss was calculated from 51Cr activity of blood and faeces. Compliance with medication was confirmed by blood sampling on days 20, 27 and 34. General tolerability of the medication was good, although 1 subject was withdrawn from piroxicam-beta-cyclodextrin and 1 from piroxicam treatment because of abdominal pain. There were no clinically significant changes in haematology, biochemistry or urinalysis results in any subject. Endoscopic appearances deteriorated moderately in 3 subjects receiving piroxicam and 3 receiving piroxicam-beta-cyclodextrin, but did not deteriorate in any subject receiving placebo. There was a trend for cumulative blood loss to be higher for piroxicam than for the other treatments in the last 12 days of dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; beta-Cyclodextrins; Chromium Radioisotopes; Cyclodextrins; Digestive System; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Endoscopy; Erythrocytes; Feces; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Male; Piroxicam

In order to evaluate the gastric tolerance of the new piroxicam formulation CHF 1194 (piroxicam complexed with beta-cyclodextrin), a double-blind randomized trial was carried out in 21 young healthy volunteers comparing CHF 1194 with piroxicam and placebo. Faecal blood loss measurement by the Cr-51 labelled red blood cell technique, upper gastrointestinal endoscopic evaluation, titration of gastric pH and gastric biopsies before, during and after treatment were used to assess drug tolerability. Four out of 7 volunteers in the piroxicam-treated group withdrew because of severe gastrointestinal symptoms and oesophageal and/or gastroduodenal lesions, while all subjects treated with CHF 1194 or placebo completed the treatment. There was a significant difference between the endoscopic scores of the piroxicam and placebo groups, whereas no differences were found between CHF 1194 and placebo, nor between piroxicam and CHF 1194. Daily mean gastrointestinal blood loss was greater in the piroxicam group than in either the CHF 1194 or placebo groups, but the difference was not significant, due to the small number of piroxicam-treated subjects who completed the study. When administered for a short period to healthy young subjects, CHF 1194 caused less gastric damage and was better tolerated than piroxicam.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Clinical Trials as Topic; Cyclodextrins; Dextrins; Double-Blind Method; Drug Combinations; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Hydrogen-Ion Concentration; Male; Piroxicam; Random Allocation; Starch