PHARMACOKINETICS AND RETROGRADE COLONIC SPREAD OF BUDESONIDE ENEMAS IN PATIENTS WITH DISTAL ULCERATIVE-COLITIS

Methods: The retrograde spread of two budesonide enema formulations wi th different viscosities was investigated, The study design was open, randomized and two-period crossover, Three female and two male patient s (age range: 35-45 years) with distal ulcerative colitis or proctitis participated, Both enema formulations contained a dose of 2 mg budeso nide/100 mL. An unabsorbable radioactive marker (Tc-99m-labelled human serum albumin microcolloid) was added to the enema just before admini stration. All doses were given in the evening with the patients lying in a supine position during the whole investigation, The intestinal sp read was followed for 8 h using scintigraphic imaging, Plasma samples for budesonide assay were taken during the 12 h after administration o f the low viscosity enema. Results: Budesonide plasma levels were meas urable for up to 4-6 h. C-max was 2.5 nmol/L (range: 0.9-4.5 nmol/L) a nd was attained in 1.5 h (range 1-3 h). The patients had no difficulty in retaining the enemas, There was a statistically significant differ ence in spread between the low and high viscosity enema. The low visco sity enema spread over an area situated between the rectum and the spl enic flexure, The spread occurred mainly in the first 15 min after adm inistration. In contrast, the high viscosity enema, in most cases, spr ead only over a minor part of this area and the rate and extent of spr eading was also more variable with this formulation. Conclusion: The s pread of a low viscosity enema appears to be well suited for the treat ment of proctitis and distal colitis.