COLONIC SPREAD OF 5-ASA ENEMAS IN HEALTHY-INDIVIDUALS, WITH A COMPARISON OF THEIR PHYSICAL AND CHEMICAL CHARACTERISTICS

Background: 5-aminosalicylic acid (5-ASA) is widely used as topical tr eatment in patients with distal inflammatory bowel disease, The enema spread and retention time are considered to be important factors in th e efficacy of this therapeutic agent. Whereas colonic spread is widely investigated in selected patient populations and volunteers, much les s attention has been given to the in vitro differences of physical and chemical properties, although they may influence the in vivo characte ristics. Methods: Two different brand enemas, Salofalk and Asacol, bot h containing 2 g mesalazine, were compared with respect to their in vi vo and in vitro characteristics. The retrograde spread, maximum distri bution and wall adhesion, as well as the retention time of the enemas, was examined by the addition of a technetium tracer dose in 12 health y volunteers on two separate occasions, In addition, several chemical properties such as pH, viscosity, particle size, dispersion rate, spec ific surface area and residual volume after application were analysed and compared. Results: With its larger volume and higher viscosity the Asacol preparation reached a substantially larger proportion of the c olon and produced a significantly higher retention time in the proxima l parts of the large intestine. In addition, more than double the amou nt of 5-aminosalicylic acid was not expelled from the semirigid Salofa lk enema container after application, With respect to chemical prop.er ties it was demonstrated that the Asacol preparation showed a signific antly smaller size of micronized 5-aminosalicylic acid particles, bett er homogeneity and much less aggregation of the drug. This resulted in an almost threefold higher specific surface area per g active compoun d. Conclusions: The Asacol enema appears to be superior in several asp ects of the galenical formulation. The better dispersion and larger sp ecific surface area, in conjunction with a larger distribution, better bowel wall adherence and retention time in vivo, constitute a clear t heoretical and possible clinical advantage.