EVALUATION OF THE EFFECT OF 3 DIFFERENT DIETS ON THE BIOAVAILABILITY OF 2 SUSTAINED-RELEASE THEOPHYLLINE MATRIX TABLETS

Food-induced changes on bioavailability of 2 sustained release theophy lline matrix tablets, which uses an hydrophilic matrix of Carbopol 974 P and a lipid matrix of hydrogenated castor oil (Cutina HR) as sustain ing agents, have been studied in 2 different groups of 12 healthy male volunteers. The study design was a 4 x 4 Latin square involving 12 su bjects who received a single dose of the tablet while fasting or with a standardized normal, high fat or high fat/high protein meal. The res ults for both formulations showed no differences in t(1/2) and MRT whe n the tablets were administered with any type of diet. No differences in t(max) and AUC were found when the Carbopol matrix tablet was admin istered with any class of diet. Higher C-max were obtained when the ta blet was administered with any class of meal. The analysis of the rati o C-max/AUC evidenced that changes in C-max for normal and high fat di et were attributable to-higher rate of absorption, probably due to a d elay in gastric emptying, thus avoiding the rapid formation of the gel structure which controls the liberation of theophylline. Three subjec ts showed a probable bioadhesive behavior of the formulation in the fa sted condition. The lipid matrix tablet showed a statistical significa nt delay in t(max) comparing the fasted condition with the different d iets. AUG, C-max, and the ratio C-max/AUC did not change when the tabl et was administered with the normal diet. High fat and high fat/high p rotein diets produced higher AUC (31% and 40%, respectively) and C-max (40% and 56%, respectively) than under fasting condition. The analysi s of the ratio C-max/AUC indicated that changes in C-max were more pro bably due to changes in the amount absorbed. In conclusion, a sustaine d-release theophylline tablet formulated as a lipid matrix is affected by any meal with a high fat content, probably because of the increase of pancreatic and biliary secretions promoted by the meal that would affect the matrix itself. Normal diet showed this behavior but only as a nonsignificant trend. It seems appropriate to recommend to dose bot h formulations at least 2 hours before meal, or under consistent condi tions of fasting or nonfasting state to assure reproducible absorption or clinical response.