Kinetics of the acid-catalyzed hydrolysis of cimetidine.
The kinetics of hydrolysis of cimetidine was studied in 0.01-1 M hydrochloric acid solutions (pH 0.15-2.15) at 37 degrees C. The hydrolytic cleavage of the cyanoguanidino group in cimetidine to give a guanylurea derivative was found to proceed quantitatively, as evidenced by HPLC analysis. The rate of hydrolysis was subject to specific acid catalysis, the specific hydrogen ion catalytic rate constant being 3.6 X 10(-3) M-1 min-1 at 37 degrees C and mu = 0.5. Increased ionic strength accelerated the rate of hydrolysis. The possible significance of the acid-catalyzed hydrolysis for the stability of cimetidine during its transit through the stomach after peroral administration was assessed. It was estimated that in the gastric pH range 1-2 and with a gastric emptying half-time of 50 min, only 0.3-2.5% of an ingested dose would be hydrolyzed in the stomach.
Buur
A
A
Bundgaard
H
H
D001682:Biological Availability; D002927:Cimetidine / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis
D002927:Cimetidine