In vitro and in vivo removal of oral antidiabetic agents (metformin) using activated carbons

摘要

Diabetes prevalence is worldwide growing at alarming rate, being of particular relevance the type 2 diabetes. This growth leads to an increasing consumption of drugs such as oral antidiabetics. Metformin is one of the active principles most commonly used for this purpose. The extensive use of this drug its highly relevant because 2 major problems have been observed: a)drug overdoses incidents; b)sewage damping in household waste. This situation is becoming a serious problem of environmental pollution and public health. This paper reports the use of activated carbon produced from biomass for the removal of metformin in 2 different settings. On one hand, from aqueous solutions (EP1) and, in another hand, from simulated biological fluids (gastric and intestinal) conjugated with in vivo testing (EP2). The activated carbon samples were produced by carbon dioxide activation at 700 and 800°C from vine shoots (V), coffee endocarp (Cf), esparto grass (E) and Eucalyptus pulp (P). Results: (EP1) The highest adsorption capacity was observed for samples P827 and E853, which reach 30 and 33mg/g, respectively. It seems that the adsorption, in this case, is determined by the porous development of the samples. (EP2) The metformin adsorption from the simulated biological gastric fluid (pH=1.2) is totally different due to the difference of the solution pH and composition. The maximum capacity to remove metformin was achieved for samples V739, P827 and E853 with approximately 130mg/g. This high capacity to capture metformin is crucial to prevent the absortion of the drug at the intestinal tract. The experiments done using the simulated intestinal fluid (pH=7.3) shown similar results to (EP1). Samples P827 and E853 were selected to perform the in vivo experiments. This work was done in 16 Wistar rats weighing 198 to 368 g, which were distributed in three groups. To Group 1 was administered the drug at a dose 600 mg/kg that corresponds to approximately 60% LD50. To Group 2 the same dose of metformin and activated carbon were administered, and finally to the third group only activated carbon was given to the animals, in the same dosage as Group 2. After oral administration there were no observed changes in animal behaviour. We have analyzed the serum and urine collected from the rats in order to study a number of biochemical indicators, such as amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and creatinine. We have observed only slight changes in two biochemical markers tested, related to renal function, which leads us to believe that it is viable to use the activated carbon samples in the treatment of drug poisoning due to its high biocompatibility. The animals of group 1 had suffered inflammation and renal dysfunction, as indicated by clearance of the creatinine. On the opposite, the animals of group 2 didn't shown symptoms of renal malfunction, which indicates that the activated carbons prevent this to occur by the adsorption of the metformin.