Pharmacokinetics and retrograde colonic spread of budesonide enemas in patients with distal ulcerative colitis

METHODS: The retrograde spread of two budesonide enema formulations with different viscosities was investigated. The study design was open, randomized and two-period crossover. Three female and two male patients (age range: 35-45 years) with distal ulcerative colitis or proctitis participated. Both enema formulations contained a dose of 2 mg budesonide/100 mL. An unabsorbable radioactive marker (99mTc-labelled human serum albumin microcolloid) was added to the enema just before administration. All doses were given in the evening with the patients lying in a supine position during the whole investigation. The intestinal spread was followed for 8 h using scintigraphic imaging. Plasma samples for budesonide assay were taken during the 12 h after administration of the low viscosity enema. RESULTS: Budesonide plasma levels were measurable for up to 4-6 h. Cmax was 2.5 nmol/L (range: 0.9-4.5 nmol/L) and was attained in 1.5 h (range 1-3 h). The patients had no difficulty in retaining the enemas. There was a statistically significant difference in spread between the low and high viscosity enema. The low viscosity enema spread over an area situated between the rectum and the splenic flexure. The spread occurred mainly in the first 15 min after administration. In contrast, the high viscosity enema, in most cases, spread only over a minor part of this area and the rate and extent of spreading was also more variable with this formulation. CONCLUSION: The spread of a low viscosity enema appears to be well suited for the treatment of proctitis and distal colitis.     

Immunological reactions of skin melanoma patients to nonspecific and adaptive immunotherapy

Patients with malignant skin melanoma were given different kinds of immunotherapy; nonspecific immunotherapy with BCG vaccine, adaptive immunotherapy with methotrexate or phytohemagglutinin activated autolymphocytes, and also a combination of polychemotherapy with BCG. The state of cell immunity was determined prior to, during and at the end of the therapy, in accordance with the courses. As a result of the conducted therapy an increased level of cell immunity was observed, that usually corresponded to clinical development of the disease. At the same time, the increase in immune response indices due to continuous administration of BCG vaccine is not related with the clinical course, while the persistent anergy or reduced level of cell immunity during this kind of therapy is a poor prognostic sign.