Effect of the interaction of drug-beta-cyclodextrin complex with bile salts on the drug absorption from rat small intestinal lumen

This investigation was concerned with the change of the bioavailability of a drug owing to the interaction of the drug-beta-cyclodextrin complex with bile salts in rat intestinal lumen. The absorption of sulfamethizole (SMZ) from rat intestinal lumen after administration of SMZ-beta-cyclodextrin complex was determined by a closed-loop method in the presence or absence of bile. The blood level of SMZ after administration of SMZ-beta-cyclodextrin complex was significantly decreased in comparison with that after administration of SMZ alone in bile duct-ligated rats. On the other hand, the blood level of SMZ after SMZ-beta-cyclodextrin administration in intact rats (bile duct non-ligated) or on the addition of sodium cholate was similar to the level in the case of SMZ alone. Thus, bile salts were found to act as a competing agent in the gastrointestinal tract.     

Modeling the absorption spectrum of tryptophan in proteins

We have applied time-dependent density functional theory (TDDFT) to study the valence pi-pi* excited states of the tryptophan chromophore in the environment of the proteins barnase and human serum albumin. The chromophore is represented by indole. Due to the approximate nature of TDDFT, in the gas phase the calculated vertical transition energies to the 1L valence states are reordered with respect to experiment. The 1L(a) state responds more than the 1L(b) state to the local environment, described fully at the TDDFT level, and to bulk environment, described by a set of point charges. Nevertheless, the vertical transitions are readily identified. For human serum albumin, our calculations predict distinct spectral characteristics between structures with different tryptophan side chain torsion angles. The computational tractability of TDDFT relative to more accurate ab initio methods allows a large part of the surrounding protein environment (up to 100 atoms) to be explicitly included in the TDDFT calculations.