KINETICS AND MECHANISM OF HYDROLYSIS OF FUROSEMIDE

Furosemide, a potent diuretic, has been found to give a low bioavailability profile when administered orally which potentially could be due to hydrolysis of the drug prior to absorption. An in vitro kinetic study was performed to elucidate the kinetics and hydrolysis mechanism of furosemide as a function of pH and temperature. In the acidic pH region, below the reported pKa of 3.8, the log K-pH profile indicated specific hydrogen ion catalysis on the undissociated species. In the basis pH region, furosemide hydrolysis is extremely slow. Using the Arrhenius parameters obtained from the studies, furosemide would have a half-life of 178 min under physiological conditions in the stomach of pH 1.0 and temperature of 37°C. © 1979.