胃内酸性条件における薬物の安定性に関する研究 Studies on Stability of Drugs under Acidic Conditions in the Stomach
Studies on Stability of Drugs under Acidic Conditions in the Stomach
抄録:Reversible hydrolytic reactions of various benzodiazepines and thienodiazepines in acidic solutions at body temperature were studied. The reactions of these drugs apparently took place at the azomethine bonds and the corresponding open-ring compounds produced were in equilibrium with the parent closed-ring compounds, but their reactivities were quite dependent on both chemical structures and the nature of substituents. The major factor influencing reactivity of azomethine bond cleavage in acidic solutions appears to be the electron density of 5-carbon. Similar results were obtained in nitrofurantoin and dantrolene. The experimental data obtained in the present study suggest that some benzodiazepines dissolved in the stomach are hydrolyzed to form the corresponding open-ring compounds because of the acidic environment in the stomach. When the open-ring compounds enter the intestine, they revert back to parent benzodiazepines due to the increase in pH value of the medium. The possible closure of the open-ring was confirmed by the detection of diazepam in serum after oral administration of the open-ring compound of diazepam to a human volunteer.