Investigation of Intestinal Absorption of Pyridinones in Rat

Recently, it has been shown that a number of hydroxypyridinones such as 1,2-dimethyl-3-hydroxypyridin-4-one (L1) are useful for the treatment of iron overload in place of desferrioxamine in thalassaemic patients. In this study, the intestinal absorption (I.A.) of L1 and one of its analogues namely 2-methy-3-hydroxypyridin-4-one (L2), which possesses a higher partition coefficient (K_part) than L1, have been determined.

The ligands L1 and L2, used in the present study, were synthesized from maltol and methylamine or ammonia, respectively in a three step reaction method. Identification and purity of compounds were achieved by spectroscopy and elemental analysis. The I.A. of drugs was determined using the Everted Gut Sac method at different concentrations and time intervals. The concentrations of samples were measured by a UV/Vis spectrophotometer (λ_max=280 nm).

The results showed that the rate and I.A. of L2 are not statistically different from those of L1. At a concentration of 60 mg/lit, and after 45 min, the absorption reached a maximum for both ligands. It is clear that for the prediction of I.A. of a new drug a simple measurement of K_part is not sufficient and other factors such as the number of hydrogen bonds between drug molecules and the surrounding molecules should also be taken into account due to their possible interferences. It could be concluded that from the point of I.A, the drug L2 has no advantage over the L1.