PHARMACOKINETIC PROPERTIES OF E3810, A NEW PROTON PUMP INHIBITOR, IN HEALTHY MALE-VOLUNTEERS

E3810 is a new H+,K+-ATPase inhibitor with a substituted benzimidazole , which is under clinical investigation for peptic ulcer treatment in Japan and the USA. Three separate studies were conducted to evaluate t he safety and to establish the pharmacokinetic profile of E3810 after oral administration to healthy male subjects. E3810 was administered a s: single oral doses (1, 3, 10, 20, 40 and 80 mg) in fasting condition s. a single oral dose (20 mg) after a meal and repeated oral doses (20 and 40 mg) once daily for 7 days. The concentrations of E3810 and its metabolites in plasma and urine were determined by HPLC methods with UV detection. E3810 was generally well tolerated by all subjects. In t he single-dose study, C-max and AUC increased with increasing doses in the dose range examined. The mean plasma half-life was about 1.0 hour and was dose-independent. The apparent oral clearance of E3810 ranged from 4.37 to 8.40 ml/min/kg. No significant deviation from linear pha rmacokinetics was observed. Approximately, 30% of a dose was excreted into the urine as thioether carboxylic acid-E3810 and its glucuronide. The mean serum protein binding was 96.3%. No effect of food intake on the C-max and AUC was observed while t(max) after a meal was 1.7 hour s longer than that in the fasting conditions. No appreciable change in drug pharmacokinetics was observed during repeated oral dosing of E38 10.